Value of cardiac magnetic resonance on the risk stratification of cardiomyopathies

Cardiomyopathies represent a diverse group of heart muscle diseases with varying etiologies,presenting a diagnostic challenge due to their heterogeneous manifestations.Regular evaluation using cardiac imaging techniques is impera-tive as symptoms can evolve over time.These imaging approaches are pivotal for accurate diagnosis,treatment planning,and optimizing prognostic outcomes.Among these,cardiovascular magnetic resonance(CMR)stands out for its ability to provide precise anatomical and functional assessments.This manuscript ex-plores the significant contributions of CMR in the diagnosis and management of patients with cardiomyopathies,with special attention to risk stratification.CMR’s high spatial resolution and tissue characterization capabilities enable early detec-tion and differentiation of various cardiomyopathy subtypes.Additionally,it offers valuable insights into myocardial fibrosis,tissue viability,and left ven-tricular function,crucial parameters for risk stratification and predicting adverse cardiac events.By integrating CMR into clinical practice,clinicians can tailor patient-specific treatment plans,implement timely interventions,and optimize long-term prognosis.The non-invasive nature of CMR reduces the need for invasive procedures,minimizing patient discomfort.This review highlights the vital role of CMR in monitoring disease progression,guiding treatment decisions,and identifying potential complications in patients with cardiomyopathies.The utilization of CMR has significantly advanced our understanding and management of these complex cardiac conditions,leading to improved patient outcomes and a more personalized approach to care.

Weighted gene co-expression network analysis reveals similarities and differences of molecular features between dilated and ischemic cardiomyopathies

Cardiomyopathies represent the most common clinical and genetic heterogeneous group of diseases that affect the heart function.Though progress has been made to elucidate the process,molecular mechanisms of different classes of cardiomyopathies remain elusive.This paper aims to describe the similarities and differences in molecular features of dilated cardiomyopathy(DCM)and ischemic cardiomyopathy(ICM).We firstly detected the co-expressed modules using the weighted gene co-expression network analysis(WGCNA).Significant modules associated with DCM/ICM were identified by the Pearson correlation coefficient(PCC)between the modules and the phenotype of DCM/ICM.The differentially expressed genes in the modules were selected to perform functional enrichment.The potential transcription factors(TFs)prediction was conducted for transcription regulation of hub genes.Apoptosis and cardiac conduction were perturbed in DCM and ICM,respectively.TFs demonstrated that the biomarkers and the transcription regulations in DCM and ICM were different,which helps make more accurate discrimination between them at molecular levels.In conclusion,comprehensive analyses of the molecular features may advance our understanding of DCM and ICM causes and progression.Thus,this understanding may promote the development of innovative diagnoses and treatments.

Cardiomyopathies:Evolution of pathogenesis concepts and potential for new therapies

Cardiomyopathies are defined as diseases of the myocardium with associated structural and functional abnormalities. Knowledge of these pathologies for a long period was not clear in clinical practice due to uncertainties regarding definition,classification and clinical diagnosis. In recent decades,major advances have been made in the understanding of the molecular and genetic issues,pathophysiology,and clinical and radiological assessment of the diseases. Progress has been made also in management of several types of cardiomyopathy. Advances in the understanding of these diseases show that cardiomyopathies represent complex entities. Here,special attention is given to evolution of classification of cardiomyopathies,with the aim of assisting clinicians to look beyond schematic diagnostic labels in order to achieve more specific diagnosis. Knowledge of the genotype of cardiomyopathies has changed the pathophysiological understanding of their etiology and clinical course,and has become more important in clinical practice for diagnosis and prevention of cardiomyopathies. New approaches for clinical and prognostic assessment are provided based on contemporary molecular mechanisms of contribution in the pathogenesis of cardiomyopathies. The genotype-phe-notype complex approach for assessment improves the clinical evaluation and management strategies of these pathologies. The review covers also the important role of imaging methods,particularly echocardiography,and cardiac magnetic resonance imaging in the evaluation of different types of cardiomyopathies. In summary,this review provides complex presentation of current state of cardiomyopathies from genetics to management aspects for cardiovascular specialists.

Role of left ventricular twist mechanics in cardiomyopathies, dance of the helices

Left ventricular twist is an essential part of left ventricular function. Nevertheless, knowledge is limited in "the cardiology community" as it comes to twist mechanics. Fortunately the development of speckle tracking echocardiography, allowing accurate, reproducible and rapid bedside assessment of left ventricular twist, has boosted the interest in this important mechanical aspect of left ventricular deformation. Although the fundamental physiological role of left ventricular twist is undisputable, the clinical relevance of assessment of left ventricular twist in cardiomyopathies still needs to be established. The fact remains; analysis of left ventricular twist mechanics has already provided substantial pathophysiological understanding on a comprehensive variety of cardiomyopathies. It has become clear that increased left ventricular twist in for example hypertrophic cardiomyopathy may be an early sign of subendocardial(microvascular) dysfunction. Furthermore, decreased left ventricular twist may be caused by left ventricular dilatation or an extensive myocardial scar. Finally, the detection of left ventricular rigid body rotation in noncompaction cardiomyopathy may provide an indispensible method to objectively confirm this difficult diagnosis. All this endorses the value of left ventricular twist in the field of cardiomyopathies and may further encourage the implementation of left ventricular twist parameters in the "diagnostic toolbox" for cardiomyopathies.

Distribution of late gadolinium enhancement in various types of cardiomyopathies:Significance in differential diagnosis, clinical features and prognosis

The recent development of cardiac magnetic resonance(CMR)techniques has allowed detailed analyses of cardiac function and tissue characterization with high spatial resolution.We review characteristic CMR features in ischemic and non-ischemic cardiomyopathies(ICM and NICM),especially in terms of the location and distribution of late gadolinium enhancement(LGE).CMR in ICM shows segmental wall motion abnormalities or wall thinning in a particular coronary arterial territory,and the subendocardial or transmural LGE.LGE in NICM generally does not correspond to any particular coronary artery distribution and is located mostly in the mid-wall to subepicardial layer.The analysis of LGE distribution is valuable to differentiate NICM with diffusely impaired systolic function,including dilated cardiomyopathy,end-stage hypertrophic cardiomyopathy(HCM),cardiac sarcoidosis,and myocarditis,and those with diffuse left ventricular(LV)hypertrophy including HCM,cardiac amyloidosis and Anderson-Fabry disease.A transient low signal intensity LGE in regions of severe LV dysfunction is a particular feature of stress cardiomyopathy.In arrhythmogenic right ventricular cardiomyopathy/dysplasia,an enhancement of right ventricular(RV)wall with functional and morphological changes of RV becomes apparent.Finally,the analyses of LGE distribution have potentials to predict cardiac outcomes and response to treatments.

Benefit of stem cells and skeletal myoblast cells in dilated cardiomyopathies

Although some authors suggest that there is mitotic division in the heart,most cardiomyocytes do not have the capacity to regenerate after myocardial infarction and when this occurs there is a deterioration of contractile function,and if the area of infarction is extensive ventricular remodeling may occur,leading to the development of heart failure.Cell transplantation into the myocardium with the goal of recovery of cardiac function has been extensively studied in recent years. The effects of cell therapy are based directly on the cell type used and the type of cardiac pathology.For myocardial ischemia in the hibernating myocardium, bone marrow cells have functional benefits,however these results in transmural fibrosis are not evident. In these cases there is a benefit of implantation with skeletal myoblasts,for treating the underlying cause of disease,the loss of cell contractility.

Role of hepatitis C virus in myocarditis and cardiomyopathies

Recent nationwide clinico-epidemiological surveys in Japan showed that the occurrence of cardiomyopathies was most frequently seen in the age of sixties, and that cardiomyopathies are important causes of heart failure in the elderly. Viral infection was conventionally considered to cause myocarditis, which resulted in the development of dilated cardiomyopathy. Recent studies suggest that hepatitis C virus (HCV) is involved in the development of dilated cardiomyopathy, hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy in addition to myocarditis. Furthermore, left ventricular aneurysm represents the same morbid state not only after myocardial infarction but also after myocarditis. There were wide variations in the frequency of detection of HCV genomes in cardiomyopathy in different regions and in different populations. Major histocompatibility complex class Ⅱ genes may play a role in the susceptibility to HCV infection, and may influence the development of different phenotypes of cardiomyopathy. If in fact the myocardial damage is caused by HCV, it might be expected that interferon (IFN) administration would be useful for its treatment. Hepatitis patients receiving IFN treatment for hepatitis were screened by thallium myocardial scintigraphy, and an abnormality was discovered in half of the patients. Treatment with IFN resulted in a disappearance of the image abnormality. It has thus been suggested that mild myocarditis and myocardial damage may be cured with IFN. We have recently found that high concentrations of circulating cardiac troponin T are a specific marker of cardiac involvement in HCV infection. By measuring cardiac troponin T in patients with HCV infection, the prevalence of cardiac involvement in HCV infection will be clarified. We are proposing a collaborative work on a global network on myocarditis/cardiomyopathies due to HCV infection. (J Geriatr Cardiol 2004;1(2):83-89. )

Impact of cardiac magnetic resonance imaging in nonischemic cardiomyopathies

Non-ischemic cardiomyopathies include a wide spectrum of disease states afflicting the heart, whether a primary process or secondary to a systemic condition. Cardiac magnetic resonance imaging(CMR) has established itself as an important imaging modality in the evaluation of non-ischemic cardiomyopathies. CMR is useful in the diagnosis of cardiomyopathy, quantification of ventricular function, establishing etiology, determining prognosis and risk stratification. Technical advances and extensive research over the last decade have resulted in the accumulation of a tremendous amount of data with regards to the utility of CMR in these cardiomyopathies. In this article, we review CMR findings of various non-ischemic cardiomyopathies and focus on current literature investigating the clinical impact of CMR on risk stratification, treatment, and prognosis.

Transient stress cardiomyopathies in the elderly： Clinical ＆ Pathophysiologic considerations

Transient stress-induced cardiomyopathies have been increasingly recognized and while rare,they tend to affect elderly women more than other demographic groups.One type,often called tako-tsubo cardiomyopathy （TTC）,is typically triggered by significant emotional or physical stress and is associated with chest pain,electrocardiogram （ECG） changes and abnormal cardiac enzymes.Significant left ventricular regional wall motion abnormalities usually include an akinetic ＂ballooning＂ apex with normal or hyperdynamic function of the base.A second type,often called neurogenic stunned myocardium,typically associated with subarachnoid hemorrhage,also usually presents with ECG changes and positive enzymes,but the typical wall motion abnormalities seen include normal basal and apical left ventricular contraction with akinesis of the mid-cavity in a circumferential fashion.The pathophysiology,clinical care and typical courses,are reviewed.

Unusual Cardiomyopathies:Some May Be More Usual Than Previously Thought and Simply Underdiagnosed

Heart failure is the most common cause of hospitalization in the United States.Just as the prevalence of heart failure has increased,the number of diseases identifi ed that result in the heart failure syndrome has escalated.Certain cardiomyopathies that have previously been regarded as very rare are being recognized with increasing frequency,because of improved imaging techniques and an increased understanding of the pathophysiologic mechanisms that result in these diseases.Improved echocardiographic techniques and methods such as spectral Doppler and 3D image rendering,along with the use of advanced diagnostic tools such as cardiac CT angiography and cardiac magnetic resonance imaging are now common.These advanced imaging methods have led to an increased appreciation of the frequency of diseases such as isolated left ventricular noncompaction and cardiac amyloidosis.Left ventricular noncompaction,once thought to occur in roughly one in one million patients,may actually be seen in fewer than one in 1000 patients.Cardiac amyloidosis,in the senile form,may exist in 80% of 80-year-old patients,although the incidence of clinical symptoms is less.As the genetic alterations that contribute to these diseases are further elucidated,improved diagnosis and a better understanding of the prognosis of these uncommon cardiomyopathies will follow.

Patient-specific induced pluripotent stem cells as“disease-in-adish”models for inherited cardiomyopathies and channelopathies–15 years of research

Among inherited cardiac conditions,a special place is kept by cardiomyopathies(CMPs)and channelopathies(CNPs),which pose a substantial healthcare burden due to the complexity of the therapeutic management and cause early mortality.Like other inherited cardiac conditions,genetic CMPs and CNPs exhibit incomplete penetrance and variable expressivity even within carriers of the same pathogenic deoxyribonucleic acid variant,challenging our understanding of the underlying pathogenic mechanisms.Until recently,the lack of accurate physiological preclinical models hindered the investigation of fundamental cellular and molecular mechanisms.The advent of induced pluripotent stem cell(iPSC)technology,along with advances in gene editing,offered unprecedented opportunities to explore hereditary CMPs and CNPs.Hallmark features of iPSCs include the ability to differentiate into unlimited numbers of cells from any of the three germ layers,genetic identity with the subject from whom they were derived,and ease of gene editing,all of which were used to generate“disease-in-a-dish”models of monogenic cardiac conditions.Functionally,iPSC-derived cardiomyocytes that faithfully recapitulate the patient-specific phenotype,allowed the study of disease mechanisms in an individual-/allele-specific manner,as well as the customization of therapeutic regimen.This review provides a synopsis of the most important iPSC-based models of CMPs and CNPs and the potential use for modeling disease mechanisms,personalized therapy and deoxyribonucleic acid variant functional annotation.

Role of genetic testing in cardiomyopathies:Αprimer for cardiologists

Recent advances in cardiovascular genetics have transformed genetic testing into a valuable part of management of families with inherited cardiomyopathies.As novel mutations have been identified,understanding when to consider genetic testing has emerged as an important consideration in the management of these cases.Specific genetic testing has a paramount importance in the risk stratification of family members,in the prognosis of probands at higher risk of a serious phenotype expression,and finally in the identification of new mutations,all of which are discussed in this review.The indications for each type of cardiomyopathy are described,along with the limitations of genetic testing.Finally,the importance of public sharing of variants in large data sets is emphasized.The ultimate aim of this review is to present key messages about the genetic testing process in order to minimize potential harms and provide suggestions to specialized clinicians who act as a part of a multidisciplinary team in order to offer the best care to families with inherited cardiomyopathies.

Hypertrophic Cardiomyopathies at the Sylvanus Olympio Teaching Hospital of Lome: Epidemiological, Diagnostic, Therapeutic and Evolutive Aspects

Background: Hypertrophic cardiomyopathy (HCM) is a form of cardiomyopathy that may involve several aspects.The aim of our study is to describe the epidemiological, diagnostic, therapeutic and short-term prognostic aspects of this form of cardiomyopathy at the Sylvanus Olympio Teaching Hospital of Lome. Materials and Methods: This was a cross-sectional study that was carried out over a four-year period from January 1, 2016 to December 31, 2019. We included in this study, patients admitted to the Cardiology Department of the Sylvanus Olympio Teaching Hospital of Lome, in whom the diagnosis of hypertrophic cardiomyopathy was retained at echocardiography in the absence of any other cause that could explain the significant hypertrophy of the walls. Results: The prevalence of hypertrophic cardiomyopathies in our study was 0.31%. The mean age of patients was 51.35 ± 15.28 years with a male predominance (sex ratio M/F of 1.22). The majority of patients (60%) were between 45 and 74 years old. The clinical presentation was dominated by congestive heart failure in 15 patients (75%). Half of the patients (50%) had type III hypertrophic cardiomyopathy according to Maron’s classification. Seven patients (35%) had obstructive HCM and the mean thickness of the interventricular septum in diastole was 15.88. Left ventricular systolic function was impaired in 40% of patients. No patient was able to do a genetic test. The combination of beta-blocker (95%), an inhibitor of the renin- angiotensin-aldosterone system (90%) and furosemide (85%) constituted the essential part of the treatment combined with Lifestyle changes. No patients have benefited from implantable cardioverter defibrillators. The yearly mortality rate at the end of our study was 70%. Conclusion: Hypertrophic cardiomyopathy remains a relatively rare pathology. It is often a late diagnosis in the context of heart failure with limited therapeutic means, explaining its heavy morbidity and mortality.

Cardiomyopathies in Tropical Countries:Causes and Nosological Perspective

Background: Cardiomyopathy is the main cause of heart failure in developing countries, mainly in Africa. In those areas the concept of “tropical cardiomyopathy” is still used to design all unexplained cardiomyopathy. The primary aim of this review is first to review the main etiologies of cardiomyopathies observed in tropical countries and second to gain a better understanding of the nosological place of the so-called “tropical cardiomyopathies” in the current framework of cardiomyopathies. Methods and Results: We reviewed relevant references over the last forty years (June, 1976 to May 2012). Given literature data, endomyocardial fibrosis (EMF) is mainly diagnosed in sub-Saharan countries, as well as Brazil and India. Peripartum cardiomyopathy (PPCM) is observed with a higher prevalence than in temperate countries. Sickle cell anemia does not induce specific cardiomyopathy in all echocardiographic studies. Malnutrition and chronic anemia can induce reversible cardiac dysfunction. Myocardial involvement in parasitic infections is restricted to Chagas disease and probably to human African trypanosomiasis. Helminthiasis is not involved in the pathogenesis of cardiomyopathy except for the deleterious effect of high eosinophilia induced by some endemic diseases (filariasis, schistosomiasis). Primary cardiomyopathies (dilated, hypertrophic, and restrictive cardiomyopathy) have no specificity. Arrhythmogenic right ventricular dysplasia and left ventricular noncompaction are also reported and do not differ from elsewhere. Conclusions: The concept of tropical cardiomyopathy is no longer relevant as most of the cardiomyopathies observed in tropical countries have no specificity, with few exceptions (PPCM, EMF, Chagas disease). In this context, the European Society of Cardiology classification offers a simpler clinical approach and allows the inclusion of the rare tropical specificities.

Teneligliptin mitigates diabetic cardiomyopathy by inhibiting activation of the NLRP3 inflammasome

BACKGROUND Diabetic cardiomyopathy(DCM),which is a complication of diabetes,poses a great threat to public health.Recent studies have confirmed the role of NLRP3(NOD-like receptor protein 3)activation in DCM development through the inflammatory response.Teneligliptin is an oral hypoglycemic dipeptidyl peptidase-IV inhibitor used to treat diabetes.Teneligliptin has recently been reported to have anti-inflammatory and protective effects on myocardial cells.AIM To examine the therapeutic effects of teneligliptin on DCM in diabetic mice.METHODS Streptozotocin was administered to induce diabetes in mice,followed by treatment with 30 mg/kg teneligliptin.RESULTS Marked increases in cardiomyocyte area and cardiac hypertrophy indicator heart weight/tibia length reductions in fractional shortening,ejection fraction,and heart rate;increases in creatine kinase-MB(CK-MB),aspartate transaminase(AST),and lactate dehydrogenase(LDH)levels;and upregulated NADPH oxidase 4 were observed in diabetic mice,all of which were significantly reversed by teneligliptin.Moreover,NLRP3 inflammasome activation and increased release of interleukin-1βin diabetic mice were inhibited by teneligliptin.Primary mouse cardiomyocytes were treated with high glucose(30 mmol/L)with or without teneligliptin(2.5 or 5μM)for 24 h.NLRP3 inflammasome activation.Increases in CKMB,AST,and LDH levels in glucose-stimulated cardiomyocytes were markedly inhibited by teneligliptin,and AMP(p-adenosine 5‘-monophosphate)-p-AMPK(activated protein kinase)levels were increased.Furthermore,the beneficial effects of teneligliptin on hyperglycaemia-induced cardiomyocytes were abolished by the AMPK signaling inhibitor compound C.CONCLUSION Overall,teneligliptin mitigated DCM by mitigating activation of the NLRP3 inflammasome.

Sodium-dependent glucose transporter 2 inhibitors effects on myocardial function in patients with type 2 diabetes and asymptomatic heart failure

BACKGROUND Sodium-dependent glucose transporter 2 inhibitors(SGLT2i)have shown efficacy in reducing heart failure(HF)burden in a very heterogeneous groups of patients,raising doubts about some contemporary assumptions of their mechanism of action.We previously published a prospective observational study that evaluated mechanisms of action of SGLT2i in patients with type 2 diabetes who were in HF stages A and B on dual hypoglycemic therapy.Two groups of patients were included in the study:the ones receiving SGLT2i as an add-on agent to metformin and the others on dipeptidyl peptidase-4 inhibitors as an add-on to metformin due to suboptimal glycemic control.AIM To evaluate the outcomes regarding natriuretic peptide,oxidative stress,inflammation,blood pressure,heart rate,cardiac function,and body weight.METHODS The study outcomes were examined by dividing each treatment arm into two subgroups according to baseline parameters of global longitudinal strain(GLS),N-terminal pro-brain natriuretic peptide,myeloperoxidase(MPO),high-sensitivity C-reactive protein(hsCRP),and systolic and diastolic blood pressure.To evaluate the possible predictors of observed changes in the SGLT2i arm during follow-up,a rise in stroke volume index,body mass index(BMI)decrease,and lack of heart rate increase,linear regression analysis was performed.RESULTS There was a greater reduction of MPO,hsCRP,GLS,and blood pressure in the groups with higher baseline values of mentioned parameters irrespective of the therapeutic arm after 6 months of follow-up.Significant independent predictors of heart rate decrease were a reduction in early mitral inflow velocity to early diastolic mitral annular velocity at the interventricular septal annulus ratio and BMI,while the predictor of stroke volume index increase was SGLT2i therapy itself.CONCLUSION SGLT2i affect body composition,reduce cardiac load,improve diastolic/systolic function,and attenuate the sympathetic response.Glycemic control contributes to the improvement of heart function,blood pressure control,oxidative stress,and reduction in inflammation.

Cardiomyopathies in China: A 2018-2019 state-of-the-art review

Cardiomyopathies are diseases of the cardiac muscle and are often characterized by ventricular dilation,hypertrophy,and cardiac arrhythmia.Patients with cardiomyopathies often experience sudden death and cardiac failure and require cardiac transplantation during the course of disease progression.Early diagnosis,differential diagnosis,and genetic consultation depend on imaging techniques,genetic testing,and new emerging diagnostic tools such as serum biomarkers.The molecular genetics of cardiomyopathies has been widely studied recently.The discovery of mechanisms underlying heterogeneity and overlapping of the phenotypes of cardiomyopathies has revealed the existence of disease modifiers,and this has led to the emergence of novel disease-modifying therapy.This 2018-2019 state-of-the-art review outlines the pathogenesis,diagnosis,and treatment of cardiomyopathies in China.

Valvular heart disease and cardiomyopathy in China:epidemiology and current treatments

The Annual Report on Cardiovascular Health and Diseases in China(2022)intricate landscape of cardiovascular health in China.In connection with the previous section,this ninth section of the report offers a comprehensive analysis of valvular heart disease and cardiomyopathy.Although rheumatic valve disease is still the main cause of valvular heart disease in China,with the aging of the population and the improvement of living standards,the prevalence of degenerative valvular heart disease is on the rise.Because many patients with valvular heart disease have only mild to moderate valve stenosis or insufficiency,and no symptoms,the detection rate in the population is low and late,resulting in many patients been in the severe late stage of disease at visit,increasing the difficulty of treatment and affecting effectiveness and prognosis.Therefore,we should strengthen the examination and screening of valvular heart disease in order to find and prevent it as early as possible.In addition,compared with other diseases,the treatment of valvular heart disease needs more and higher technical support(surgery,intervention,etc).However,not all hospitals can provide relevant technologies.At present,the treatment of valvular heart disease is still mainly concentrated in the provincial hospitals.It is necessary to carry out more professional training so that more doctors and hospitals can participate in the treatment of valvular heart disease.Cardiomyopathy is a group of myocardial diseases with abnormal myocardial structure and/or function,but couldn't be explained by hypertension,coronary atherosclerosis,valvular heart disease and congenital heart disease.It includes hypertrophic cardiomyopathy(HCM),dilated cardiomyopathy(DCM),arrhythmogenic cardiomyopathy(also known as arrhythmogenic right ventricular cardiomyopathy),restrictive cardiomyopathy(RCM)and undifferentiated cardiomyopathy.

Adipsin inhibits Irak2 mitochondrial translocation and improves fatty acid β-oxidation to alleviate diabetic cardiomyopathy

Background Diabetic cardiomyopathy (DCM) causes the myocardium to rely on fatty acid β-oxidation for energy. The accumulation of intracellular lipids and fatty acids in the myocardium usually results in lipotoxicity, which impairs myocardial function. Adipsin may play an important protective role in the pathogenesis of DCM. The aim of this study is to investigate the regulatory effect of Adipsin on DCM lipotoxicity and its molecular mechanism.MethodsA high-fat diet (HFD)-induced type 2 diabetes mellitus model was constructed in mice with adipose tissue-specific overexpression of Adipsin (Adipsin-Tg). Liquid chromatography-tandem mass spectrometry (LC–MS/MS), glutathione-S-transferase (GST) pull-down technique, Co-immunoprecipitation (Co-IP) and immunofluorescence colocalization analyses were used to investigate the molecules which can directly interact with Adipsin. The immunocolloidal gold method was also used to detect the interaction between Adipsin and its downstream modulator.ResultsThe expression of Adipsin was significantly downregulated in the HFD-induced DCM model (P < 0.05). Adipose tissue-specific overexpression of Adipsin significantly improved cardiac function and alleviated cardiac remodeling in DCM (P < 0.05). Adipsin overexpression also alleviated mitochondrial oxidative phosphorylation function in diabetic stress (P < 0.05). LC–MS/MS analysis, GST pull-down technique and Co-IP studies revealed that interleukin-1 receptor-associated kinase-like 2 (Irak2) was a downstream regulator of Adipsin. Immunofluorescence analysis also revealed that Adipsin was co-localized with Irak2 in cardiomyocytes. Immunocolloidal gold electron microscopy and Western blotting analysis indicated that Adipsin inhibited the mitochondrial translocation of Irak2 in DCM, thus dampening the interaction between Irak2 and prohibitin (Phb)-optic atrophy protein 1 (Opa1) on mitochondria and improving the structural integrity and function of mitochondria (P < 0.05). Interestingly, in the presence of Irak2 knockdown, Adipsin overexpression did not further alleviate myocardial mitochondrial destruction and cardiac dysfunction, suggesting a downstream role of Irak2 in Adipsin-induced responses (P < 0.05). Consistent with these findings, overexpression of Adipsin after Irak2 knockdown did not further reduce the accumulation of lipids and their metabolites in the cardiac myocardium, nor did it enhance the oxidation capacity of cardiomyocytes expose to palmitate (PA) (P < 0.05). These results indicated that Irak2 may be a downstream regulator of Adipsin.ConclusionsAdipsin improves fatty acid β-oxidation and alleviates mitochondrial injury in DCM. The mechanism is related to Irak2 interaction and inhibition of Irak2 mitochondrial translocation.

Jianpi Qinghua Formula Alleviates Diabetic Myocardial Injury Through Inhibiting JunB/c-Fos Expression

Objective Diabetic cardiomyopathy(DCM)represents a substantial risk factor for heart failure and increased mortality in individuals afflicted with diabetes mellitus(DM).DCM typically manifests as myocardial fibrosis,myocardial hypertrophy,and impaired left ventricular diastolic function.While the clinical utility of the Jianpi Qinghua(JPQH)formula has been established in treating diabetes and insulin resistance,its potential efficacy in alleviating diabetic cardiomyopathy remains uncertain.This study aims to investigate the impact and underlying molecular mechanisms of the JPQH formula(JPQHF)in ameliorating myocardial injury in nonobese diabetic rats,specifically focusing on apoptosis and inflammation.Methods Wistar rats were assigned as the normal control group(CON),while Goto-Kakizaki(GK)rats were randomly divided into three groups:DM,DM treated with the JPQHF,and DM treated with metformin(MET).Following a 4-week treatment regimen,various biochemical markers related to glucose metabolism,cardiac function,cardiac morphology,and myocardial ultrastructure in GK rats were assessed.RNA sequencing was utilized to analyze differential gene expression and identify potential therapeutic targets.In vitro experiments involved high glucose to induce apoptosis and inflammation in H9c2 cells.Cell viability was evaluated using CCK-8 assay,apoptosis was monitored via flow cytometry,and the production of inflammatory cytokines was measured using quantitative real-time PCR(qPCR)and ELISA.Protein expression levels were determined by Western blotting analysis.The investigation also incorporated the use of MAPK inhibitors to further elucidate the mechanism at both the transcriptional and protein levels.Results The JPQHF group exhibited significant reductions in interventricular septal thickness at end-systole(IVSs)and left ventricular internal diameter at end-systole and end-diastole(LVIDs and LVIDd).JPQHF effectively suppressed high glucose-induced activation of IL-1βand caspase 3 in cardiomyocytes.Furthermore,JPQHF downregulated the expression of myocardial JunB/c-Fos,which was upregulated in both diabetic rats and high glucose-treated H9c2 cells.Conclusion The JPQH formula holds promise in mitigating diabetic myocardial apoptosis and inflammation in cardiomyocytes by inhibiting JunB/c-Fos expression through suppressing the MAPK(p38 and ERK1/2)pathway.