Adherence to Pharmacotherapy in Post-Menopausal Women with Hypertension or Metabolic Syndrome: Real World Experience

Background: Adherence to medications is dependent upon a variety of factors, including individual characteristics of the patient, interactions with health care providers, and medication complexity. Even though several studies were conducted to test intervention strategies, results are uncertain. Aim: The aim of the study is to assess if a tailored combined intervention strategy improves medication adherence in a large population of post-menopausal women affected by hypertension or metabolic syndrome. Methods: We enrolled 6833 patients aged 50 to 69 years, 85.7% with hypertension, and 14.3% with metabolic syndrome. A network between patients, general practitioners, and cardiologists was established. Interventions included education, adequate information to patients, a simplified scheme of treatment, and periodic adherence assessment. These were either delivered as healthcare provider supports or using modern technology. Medication adherence was estimated by the proportion of days covered for all classes of drugs after the index date. Results: Non-adherent hypertensive women were 297 (5%), and those with metabolic syndrome were 73 (7.4%) (p Conclusions: The rate of non-adherence in both settings of postmenopausal women was 7.7%, much lower than that described in the literature. This rate was increased in patients with metabolic syndrome;probably it is related to the complexity of the therapeutic scheme or to a poor consciousness of the disease. Therefore, implementing a tailored combined intervention can improve significantly patients’ adherence to medical therapy.

Osthole attenuates pulmonary arterial hypertension by modulation of phospholipid metabolism

OBJECTIVE Pulmonary arterial hypertension(PAH)is a malignant pulmonary vascular disease lacking efficacy therapeutics.Therefore,it urgently needs to develop safe and effective drugs for PAH treatment.Osthole derived from Cnidium monnieri(L.)Cusson(Shechuangzi)or Angelica pubescens Maxim(Duhuo)has the capacity to alleviate PAH by decreasing pulmonary arterial pressure and alleviating pulmonary vascular remodeling in rats,which is a candidate drug for the prevention of PAH,but the underlying modulatory mechanism is still unclear.Our study aims at investigating the metabolic modulatory mechanism of osthole against PAH employing functional metabolomics strategy.METHODS PAH model rats were successfully established with MCT,following osthole administration,then functional metabolomics based on untargeted metabolomics assay,targeted lipidomics analysis,qRT-PCR,Western blotting and ELISA were performed to investigate the modulatory mechanism of osthole against pulmonary arterial pressure and pulmonary vascular remodeling in PAH.RESULTS Untargeted metabolomics results found that sphingosine 1-phosphate(S1P)was the differential metabolites characterized PAH and reversed by osthole treatment.S1P is a crucial sphingolipid metabolite catalyzed by sphingosine kinases1(Sphk1)and functions as promoting PASMCs proliferation contributing to pulmonary vascular remodeling and pulmonary arterial pressure increase.We revealed that osthole reversed high level of S1P by modulating metabolic enzyme Sphk1 via inactivating microRNA-21-PI3K/Akt/mTOR signal pathway to decrease pulmonary arterial pressure in rats with PAH.Then,targeted phospholipid metabolomics results uncovered that decadienyl-L-carnitine(C10:2)was the differential metabolite characterized PAH and corrected by osthole treatment in rat with PAH.C10:2 is the intermediate metabolite of fatty acid oxidation(FAO),and C10:2 accumulation indicated mitochondrial dysfunction and FAO increase.CONCLUSION Osthole could block lipid metabolic reprogramming through functional modulating the expression of fatty acid translocase,fatty acid synthase,phospholipase A2,carnitine palmitoyltransferase 1A to inhibit C10:2,thus to improve mitochondrial dysfunction and inhibit utilizing lipid to biosynthesize necessary essence for pulmonary artery smooth muscle cells(PASMCs)proliferation.Moreover,we delineated that C10:2 and metabolic reprogramming enzymes were modulated by miRNA-22-3p which was involved in PASMCs proliferation and pulmonary vascular remodeling.Therefore,osthole inhibited miRNA-22-3p mediated lipid metabolic reprogramming to ameliorate pulmonary vascular remodeling.

Antihypertensive drugs and glucose metabolism

Hypertension plays a major role in the development and progression of micro-and macrovascular disease.Moreover,increased blood pressure often coexists with additional cardiovascular risk factors such as insulin resistance.As a result the need for a comprehensive management of hypertensive patients is critical.However,the various antihypertensive drug categories have different effects on glucose metabolism.Indeed,angiotensin receptor blockers as well as angiotensin converting enzyme inhibitors have been associated with beneficial effects on glucose homeostasis.Calcium channel blockers(CCBs)have an overall neutral effect on glucose metabolism.However,some members of the CCBs class such as azelnidipine and manidipine have been shown to have advantageous effects on glucose homeostasis.On the other hand,diuretics andβ-blockers have an overall disadvantageous effect on glucose metabolism.Of note,carvedilol as well as nebivolol seem to differentiate themselves from the rest of theβ-blockers class,being more attractive options regarding their effect on glucose homeostasis.The adverse effects of some blood pressure lowering drugs on glucose metabolism may,to an extent,compromise their cardiovascular protective role.As a result the effects on glucose homeostasis of the various blood pressure lowering drugs should be taken into account when selecting an antihypertensive treatment,especially in patients which are at high risk for developing diabetes.

Pulmonary hypertension and metabolic syndrome: Possible connection, PPARγ and Caveolin-1

A number of disparate diseases can lead to pulmonary hypertension(PH), a serious disorder with a high morbidity and mortality rate. Recent studies suggest that the associated metabolic dysregulation may be an important factor adversely impacting the prognosis of PH. Furthermore, metabolic syndrome is associated with vascular diseases including PH. Inflammation plays a significant role both in PH and metabolic syndrome. Adipose tissue modulates lipid and glucose metabolism, and also produces pro-and anti-inflammatory adipokines that modulate vascular function and angiogenesis, suggesting a close functional relationship between the adipose tissue and the vasculature. Both caveolin-1, a cell membrane scaffolding protein and peroxisome proliferator-activated receptor(PPAR) γ, a ligandactivated transcription factor are abundantly expressed in the endothelial cells and adipocytes. Both caveolin-1 and PPARγ modulate proliferative and anti-apoptotic pathways, cell migration, inflammation, vascular homeostasis, and participate in lipid transport, triacylglyceride synthesis and glucose metabolism. Caveolin-1 and PPARγ regulate the production of adipokines and in turn are modulated by them. This review article summarizes the roles and inter-relationships of caveolin-1,PPARγ and adipokines in PH and metabolic syndrome.

Metabolic and genetic assessments interpret unexplained aggressive pulmonary hypertension induced by methylmalonic acidemia:A case report

BACKGROUND Pulmonary hypertension (PH) causes significant morbidity and mortality in diverse childhood diseases.However,limited information has been reported to obtain a good understanding of pediatric PH.Gaps exist between genome sequencing and metabolic assessments and lead to misinterpretations of the complicated symptoms of PH.Here,we report a rare case of a patient who presented with severe PH as the first manifestation without significant cardiovascular malformation and was finally diagnosed with methylmalonic aciduria (MMA) after metabolic and genomic assessments.CASE SUMMARY An 11-year-old female presented with an aggressive reduction in activity capability and shortness of breath for only 4 mo and suffered from unexplained PH.A series of examinations was performed to evaluate any possible malformations or abnormalities of the cardiovascular system and lungs,but negative results were obtained.The blood tests were normal except for manifestations of microcytic anemia and elevated total homocysteine.Computed tomography and magnetic resonance imaging failed to identify any pulmonary diseases.Cardiac catheterization examination identified a small right coronary artery to pulmonary artery shunt and severe PH.During the follow-up,PH progressed rapidly.Then,genome sequencing and metabolic disorder screening were performed,which confirmed a diagnosis of MMA with MMACHC c.80A>G/c and 609G> A mutations.Vitamin B12,betaine and bosentan were then administered as the main treatments.During the 6-mo follow-up,the pulmonary artery pressure dropped to 45 mmHg,while the right ventricle structure recovered.The patient’s heart function recovered to NYHA class Ⅱ.Metabolic disorder analysis failed to identify significant abnormalities.CONCLUSION As emerging types of metabolic dysfunction have been shown to present as the first manifestation of PH,and taking advantage of next generation sequencing technology,genome sequencing and metabolic disorder screening are recommended to have a more superior role when attempting to understand unclear or aggressive PH.

Vascular Metabolic Mechanisms of Pulmonary Hypertension

Pulmonary hypertension(PH)is a severe and progressive disease characterized by increased pulmonary vascular resistance leading to right heart failure and death.In PH,the cellular metabolisms including those of the three major nutrients(carbohydrate,lipid and protein)are aberrant in pulmonary vascular cells.Glucose uptake,glycolysis,insulin resistance,sphingolipid S1P,PGE2,TXA2,leukotrienes and glutaminolysis are upregulated,and phospholipid-prostacyclin and L-arginine-nitric oxide pathway are compromised in lung vascular cells.Fatty acid metabolism is disordered in lung endothelial cells and smooth muscle cells.These molecular mechanisms are integrated to promote PH-specific abnormal vascular cell proliferation and vascular remodeling.This review summarizes the recent advances in the metabolic reprogramming of glucose,fatty acid,and amino acid metabolism in pulmonary vascular remodeling in PH and the mechanisms for how these alterations affect vascular cell fate and impact the course of PH.

Investigating causal links between gastroesophageal reflux disease and essential hypertension

Gastroesophageal reflux disease(GERD)is a prevalent global health concern with a rising incidence.Various risk factors,including obesity,hiatal hernia,and smo-king,contribute to its development.Recent research suggests associations bet-ween GERD and metabolic syndrome,cardiac diseases,and hypertension(HTN).Mechanisms linking GERD to HTN involve autonomic dysfunction,inflammatory states,and endothelial dysfunction.Furthermore,GERD medications such as pro-ton-pump inhibitors may impact blood pressure regulation.Conversely,antihy-pertensive medications like beta-blockers and calcium channel blockers can exacerbate GERD symptoms.While bidirectional causality exists between GERD and HTN,longitudinal studies are warranted to elucidate the precise relationship.Treatment of GERD,including anti-reflux surgery,may positively influence HTN control.However,the interplay of lifestyle factors,comorbidities,and medications necessitates further investigation to comprehensively understand this relation-ship.In this editorial,we comment on the article published by Wei et al in the recent issue of the World Journal of Clinical Cases.We evaluate their claims on the causal association between GERD and HTN.

Obesity, hypertension and the metabolic syndrome

The prevalence of obesity in both developed and developing countries has increased dramatically in recent years.1Many people who are obese develop metabolic changes that increase the risk of diabetes mellitus and adverse cardiovascular outcomes. Obesity leads to the development of insulin resistance, lipid abnormalities and increased blood pressure.……

Association of ACE Gene with Metabolic Syndrome, Hypertension and Alzheimer Disease by RFLP-PCR

ACE gene is associated with multifactorial diseases:metabolic syndrome,obesity,diabetes mellitus,hypertension,stroke,myocardial infarction,ageing,Alzheimer disease,acute pulmonary failure and COVID-19 infections.The purpose of this study is to test the association between the II,ID and DD polymorphisms of angiotensin-converting enzyme(ACE)gene,and metabolic syndrome,hypertension(HBP)and Alzheimer disease(AD),based on clinical data and biochemical laboratory investigations conducted on inpatients,applying the RFLP-PCR technique.The genotyping of ACE gene was carried out by RFLP-PCR on the basis of DNA isolated from total blood in 144 subjects selected at Giurgiu County Emergency Hospital.The results were statistically processed by the Hardy-Weinberg equilibrium,Odds Ratio,VMD,StatsDirect and PyElph software.The II,ID and DD polymorphisms of ACE gene identified by the RFLP-PCR present a high risk of developing the metabolic syndrome in the MS,hypertension and Alzheimer disease groups.

Anti-hypertensive effects of rosiglitazone on renovascular hypertensive rats:role of oxidative stress and lipid metabolism

This study investigated the anti-hypertensive mechanismof rosiglitazone in renovascular hypertensive rats,and examined its relationship to oxidative stress and lipid metabolism. The renovascular hypertension was induced by stenosis of the left renal artery. Four groups of rats were selected： control,induced untreated,rosiglitazone（ 20 mg / kg） and captopril（ 10 mg / kg）. After 14 d of administration,compared with induced untreated group,rosiglitazone group reduced the renovascular hypertensive rats ＇ systolic blood pressure and diastolic blood pressure,and decreased total cholesterol（TCH）,triglyceride（TG）,angiotensin II（ Ang II） and angiotensin receptor（ AT1） levels（ P ＆lt; 0. 05）. Meanwhile,rosiglitazone remarkably decreased the levels of malondialdehyde（ MDA） and hydrogen peroxide（ H2O2） while improved the levels of supperoxide dismutase（ SOD） and reduced glutathione（ GSH）. These results suggested that rosiglitazone could effectively decreased the blood pressure in renovascular hypertensive rats,and this might be performed by regulating the activity of angiotensin and the lipid metabolismand improving the oxidative stress.

Metabolically healthy obesity increase risk for hypertension,T2DM and the metabolic syndrome:A community-based cohort study

Objective:To investigate the prevalence of metabolically healthy obesity(MHO)and its relationship with incidence of metabolic syndrome(MetS),type 2diabetes mellitus(T2DM)and hypertension in individuals in the city of Yulin.Methods:We studied 1,666 participants,aged over18years at baseline,with free of components of the MetS except waist criteria.Participants were divided into three groups based on body mass index(Ibm):lean/normal weight(Ibm<23kg/m2),overweight(Ibm,23-24.9kg/m2),obesity(Ibm≥25 kg/m2).The cumulative incidence of MetS,T2DM and hypertension over 5.21years among groups was assessed.Results:The prevalence of MHO was 19.5%in the baseline population.During an average 5.21year follow-up,the cumulative incidence of MetS,T2DM and hypertension in1,666participants were 16.4%,19.1%and 3.9%,respectively.The obesity group had a significantly higher cumulative incidence of MetS(16.4%vs.3.2%,P<0.001),hypertension(19.1%vs.3.7%,P<0.001),and T2DM(3.9%vs.1.6%,P<0.001)compared to the lean/normal weight group.Each kg/m2 of Ibm carried increased risk for T2DM(19%),hypertension(11%)and MetS(13%).Conclusion:Metabolically healthy obesity individuals confer increased risk for hypertension,T2DM and the MetS than their non-obese counterparts.

Effects of Chinese herbal medicine Yiqi Huaju Formula on hypertensive patients with metabolic syndrome:a randomized,placebo-controlled trial

BACKGROUND： Patients with hypertension coupled with metabolic syndrome （MetS） are among the high risk population in cardiovascular and cerebrovascular diseases. To reduce the prevalence of cardiovascular and cerebrovascular diseases, it is essential to appropriately control b^ood pressure together with other cardiovascular risk factors. OBJECTIVE： The current study was designed to investigate the therapeutic effects on blood pressure, blood pressure variability and other cardiovascular risk factors by giving Yiqi Huaju Formula, a compound traditional Chinese herbal medicine, in addition to routine treatment to hypertensive patients coupled with MetS. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS： A total of 43 patients with hypertension coupled with MetS were recruited into this study. The enrolled patients were randomly divided into the Chinese herbal formula group （anti-hypertensive drugs plus Yiqi Huaju Formula, CHF） and the control group （anti-hypertensive drugs plus placebo）. The CHF group enrolled 22 patients while the control group received 21 cases. Treatments were given for 12 weeks in both groups. MAIN OUTCOME MEASURES： Parameters examined include 24-hour ambulatory blood pressure monitoring, body mass index, waist circumference, waist-to-hip ratio, homeostatic model assessment for insulin resistance （HOMA-IR）, fasting glycosylated hemoglobin （HbAlc）, fasting plasma glucose, 2-hour postprandial plasma glucose （PPG）, fasting plasma insulin, serum lipid, etc. RESULTS： Compared with the control group, the CHF group had significant improvement （P〈0.01） in anthropometric parameters, FPG, HOMA-IR, blood pressure amplitude, blood pressure variability and blood pressure load. CONCLUSION： This study showed that integrated traditional Chinese and Western medicine treatment can achieve better results in controlling blood pressure as well as other cardiovascular risk factors. The mechanism of controlling of blood pressure may be associated with the improvement of insulin sensitivity due to the Yiqi Huaju intervention. TRIAL REGISTRATION IDENTIFIER： ChiCTR-TRC-11001633.

Metabolic syndrome in hypertensive patients:An unholy alliance

For many years, it has been recognized that hypertension tends to cluster with various anthropometric and metabolic abnormalities including abdominal obesity, elevated triglycerides, reduced high-density lipoprotein cholesterol, glucose intolerance, insulin resistance and hyperuricemia. This constellation of various conditions has been transformed from a pathophysiological concept to a clinical entity, which has been defined metabolic syndrome(MetS). The consequences of the MetS have been difficult to assess without commonly accepted criteria to diagnose it. For this reason, on 2009 the International Diabetes Federation, the American Heart Association and other scientific organizations proposed a unified MetS definition. The incidence of the MetS has been increasing worldwide in parallel with an increase in overweight and obesity. The epidemic proportion reached by the MetS represents a major public health challenge, because several lines of evidence showed that the MetS, even without type 2 diabetes, confers an increased risk of cardiovascular morbidity and mortality in different populations including also hypertensive patients. It is likely that the enhanced cardiovascular risk associated with MetS in patients with high blood pressure may be largely mediated through an increased prevalence of preclinical cardiovascular and renal changes, such as left ventricular hypertrophy, early carotid atherosclerosis, impaired aortic elasticity, hypertensive retinopathy and microalbuminuria. Indeed, many reports support this notion, showing that hypertensive patients with MetS exhibit, more often than those without it, these early signs of end organ damage, most of which are recognized as significant independent predictors of adverse cardiovascular outcomes.

Effects of Impaired Glucose Metabolism on Heart Rate Variability and Blood Pessure Variability in Essential Hpertensive Patients

To investigate the effects of impaired glucose metabolism （IGM） on cardiovascular autonomic nervous systems in essential hypertensive （EH） patients by comparing heart rate variability （HRV） and blood pressure variability （BPV） in EH patients with or without type 2 diabetes mellitus （T2DM）. Simultaneous 24-h recordings of ambulatory ECG and blood pressure monitoring were performed in 36 male old patients with simple EH and 33 male old patients with EH combined with T2DM. HRV analysis included time domain parameters such as SDNN, SDANN, SDNNi, rMSSD and pNN50, and total spectral power （TP） of HRV, which mainly consists of VLF, LF and HF component along with LF/HF ratio, was also obtained. The value of ambulatory blood pressure was represented as the mean blood pressure （mean systolic/mSBP, diastolic/mDBP and pulse pressure/mPP） during different periods （24 h/24 h, day time/d and night time/n）. Standard deviation （SD） as well as coefficient of variance （CV） of blood pressure during each above-mentioned period were obtained to reflect the long-term BPV. Our result showed that SDNN, SDNNi, SDANN, rMSSD, PNN50, TP and HF of HRV in cases of EH with T2DM were all significantly lower than those in simple EH subjects （P〈0.05）. No significant differences in VLF or LF was found between the two groups （P〉0.05）, while LF/HF ratio was significantly higher in EH with T2DM patients than in simple EH subjects （P〈0.01）. Moreover, dmSBP, 24 h-mPP and dmPP were all significantly higher in EH with T2DM patients than in simple EH subjects （P〈0.05）, while nmSBP, 24 h-mSBP, 24 h-mDBP, dmDBP, nmDBP or nmPP showed no significant difference between this two groups of patients （P〉0.05）. And dSBPSD, dSBPCV and 24 h-SBPSD were all significantly higher in EH with T2DM patients than in simple EH subjects （P〈0.05）, while the other BPV indexes showed no significant difference between this two groups （P〉0.05）. It is concluded that the cardiovascular autonomic nervous systems in EH patients was further impaired by T2DM, displaying lowering of HRV and enlargement of BPV, which in turn induced abnormal structural and functional changes of cardiovascular systems. Therefore, improving cardiovascular autonomic nervous systems might reduce the occurrence of cardiovascular complications in the EH patients with IGM.

Analysis of the nitric oxide-cyclic guanosine monophosphate pathway in experimental liver cirrhosis suggests phosphodiesterase-5 as potential target to treat portal hypertension

AIM To investigate the potential effect of inhibitors of phosphodiesterase-5(PDE-5) for therapy of portal hypertension in liver cirrhosis.METHODS In the rat model of thioacetamide-induced liver fibrosis/cirrhosis the nitric oxide-cyclic guanosine monophosphate(NO-cGMP) pathway was investigated. Expression and localization of PDE-5, the enzyme that converts vasodilating cGMP into inactive 5'-GMP, was in the focus of the study. Hepatic gene expression of key components of the NO-cGMP pathway was determined by qRT-PCR: Endothelial NO synthase(eNOS), inducible NO synthase(iNOS), soluble guanylate cyclase subunits α1 and β1(sGCa1, sGCb1), and PDE-5. Hepatic PDE-5 protein expression and localization were detected by immunohistochemistry. Serum cGMP concentrations were measured using ELISA. Acute effects of the PDE-5 inhibitor Sildenafil(0.1 mg/kg or 1.0 mg/kg) on portal and systemic hemodynamics were investigated using pressure transducers.RESULTS Hepatic gene expression of eNOS(2.2-fold; P = 0.003), sGCa1(1.7-fold; P = 0.003), sGCb1(3.0-fold; P = 0.003), and PDE-5(11-fold; P = 0.003) was increased in cirrhotic livers compared to healthy livers. Overexpression of PDE-5(7.7-fold; P = 0.006) was less pronounced in fibrotic livers. iNOS expression was only detected in fibrotic and cirrhotic livers. In healthy liver, PDE-5 protein was localized primarily in zone 3 hepatocytes and to a lesser extent in perisinusoidal cells. This zonation was disturbed in cirrhosis: PDE-5 protein expression in perisinusoidal cells was induced approximately 8-fold. In addition, PDE-5-expressing cells were also found in fibrous septa. Serum cGMP concentrations were reduced in rats with cirrhotic livers by approximately 40%. Inhibition of PDE-5 by Sildenafil caused a significant increase in serum cGMP concentrations [+ 64% in healthy rats(P = 0.024), + 85% in cirrhotic rats(P = 0.018)]. Concomitantly, the portal venous pressure was reduced by 19% in rats with liver cirrhosis. CONCLUSION Overexpression and abrogated zonation of PDE-5 likely contribute to the pathogenesis of cirrhotic portal hypertension. PDE-5 inhibition may therefore be a reasonable therapeutic approach for portal hypertension.

Way back for fructose and liver metabolism:Bench side to molecular insights

The World Health Organization recommends that the daily intake of added sugars should make up no more than 10% of total energy.The consumption of sugarsweetened beverages is the main source of added sugars.Fructose,together with glucose,as a component of high fructose corn syrups or as a component of the sucrose molecule,is one of the main sweeteners present in this kind of beverages.Data from prospective and intervention studies clearly point to high fructose consumption,mainly in the form of sweetened beverages,as a risk factor for several metabolic diseases in humans.The incidence of hypertension,nonalcoholic fatty liver disease(NAFLD),dyslipidemia(mainly hypertriglyceridemia),insulin resistance,type 2 diabetes mellitus,obesity,and the cluster of many of these pathologies in the form of metabolic syndrome is higher in human population segments that show high intake of fructose.Adolescent and young adults from lowincome families are especially at risk.We recently reviewed evidence from experimental animals and human data that confirms the deleterious effect of fructose on lipid and glucose metabolism.In this present review we update the information generated in the past 2 years about high consumption of fructose-enriched beverages and the occurrence of metabolic disturbances,especially NAFLD,type 2 diabetes mellitus,and metabolic syndrome.We have explored recent data from observational and experimental human studies,as well as experimental data from animal and cell models.Finally,using information generated in our laboratory and others,we provide a view of the molecular mechanisms that may be specifically involved in the development of liver lipid and glucose metabolic alterations after fructose consumption in liquid form.

Implication of proliferation gene biomarkers in pulmonary hypertension

Objective/Background:Proliferation is a widely recognized trigger for pulmonary hypertension(PH),a life-threatening,progressive disorder of pulmonary blood vessels.This study was aimed to identify some proliferation associated genes/targets for better comprehension of PH pathogenesis.Methods:Human pulmonary arterial smooth muscle cells(hPASMCs)were cultured in the presence or absence of human recombinant platelet derived growth factor(rhPDGF)-BB.Cells were collected for metabolomics or transcriptomics study.Gene profiling of lungs of PH rats after hypoxia exposure or of PH patients were retrieved from GEO database.Results:90 metabolites(VIP score>1,fold change>2 or<0.5 and p<.05)and 2701 unique metabolism associated genes(MAGs)were identified in rhPDGF-BB treated hPASMCs compared to control cells.In addition,1151 differentially expressed genes(313 upregulated and 838 downregulated)were identified in rhPDGF-BB treated hPASMCs compared to control cells(fold change>2 or<0.5 and p<.05).152 differentially expressed MAGs were then determined,out of which 9 hub genes(IL6,CXCL8,CCL2,CXCR4,CCND1,PLAUR,PLAU,HBEGF and F3)were defined as core proliferation associated hub genes in protein proten interaction analysis.In addition,the hub gene-based LASSO model can predict the occurrence of PH(AUC=0.88).The expression of CXCR4,as one of the hub genes,was positively correlated to immune cell infiltrates.Conclusion:Our findings revealed some key proliferation associated genes in PH,which provide the crucial information concerning complex metabolic reprogramming and inflammatory modulation in response to proliferation signals and might offer therapeutic gains for PH.

Animal models of pulmonary hypertension due to left heart disease

Pulmonary hypertension due to left heart disease(PH-LHD) is regarded as the most prevalent form of pulmonary hypertension(PH). Indeed, PH is an independent risk factor and predicts adverse prognosis for patients with left heart disease(LHD). Clinically, there are no drugs or treatments that directly address PH-LHD, and treatment of LHD alone will not also ameliorate PH. To target the underlying physiopathological alterations of PH-LHD and to develop novel therapeutic approaches for this population, animal models that simulate the pathophysiology of PH-LHD are required. There are several available models for PH-LHD that have been successfully employed in rodents or large animals by artificially provoking an elevated pressure load on the left heart, which by transduction elicits an escalated pressure in pulmonary artery. In addition, metabolic derangement combined with aortic banding or vascular endothelial growth factor receptor antagonist is also currently applied to reproduce the phenotype of PH-LHD. As of today, none of the animal models exactly recapitulates the condition of patients with PH-LHD. Nevertheless, the selection of an appropriate animal model is essential in basic and translational studies of PH-LHD. Therefore, this review will summarize the characteristics of each PH-LHD animal model and discuss the advantages and limitations of the different models.

Impact of metabolic syndrome components on clinical outcomes in hypertriglyceridemia-induced acute pancreatitis

BACKGROUND The incidence of hypertriglyceridemia(HTG)-induced acute pancreatitis(AP)is steadily increasing in China,becoming the second leading cause of AP.Clinical complications and outcomes associated with HTG-AP are generally more severe than those seen in AP caused by other etiologies.HTG-AP is closely linked to metabolic dysfunction and frequently coexists with metabolic syndrome or its components.However,the impact of metabolic syndrome components on HTGAP clinical outcomes remains unclear.AIM To investigate the impact of metabolic syndrome component burden on clinical outcomes in HTG-AP.METHODS In this retrospective study of 255 patients diagnosed with HTG-AP at the First Affiliated Hospital of Guangxi Medical University,we collected data on patient demographics,clinical scores,complications,and clinical outcomes.Subsequently,we analyzed the influence of the presence and number of individual metabolic syndrome components,including obesity,hyperglycemia,hypertension,and low high-density lipoprotein cholesterol(HDL-C),on the aforementioned parameters in HTG-AP patients.RESULTS This study found that metabolic syndrome components were associated with an increased risk of various complications in HTG-AP,with low HDL-C being the most significant risk factor for clinical outcomes.The risk of complications increased with the number of metabolic syndrome components.Adjusted for age and sex,patients with highcomponent metabolic syndrome had significantly higher risks of renal failure[odds ratio(OR)=3.02,95%CI:1.12-8.11)],SAP(OR=5.05,95%CI:2.04-12.49),and intensive care unit admission(OR=6.41,95%CI:2.42-16.97)compared to those without metabolic syndrome.CONCLUSION The coexistence of multiple metabolic syndrome components can synergistically worsen the clinical course of HTGAP,making it crucial to monitor these components for effective disease management.

Altered Liver Gene Expression Due to Hypertension and Age in Rats

Hypertension and metabolic syndrome, both of which increase with age, are multifactorial disorders. Their etiology is complex, making it challenging to isolate involved genes. This study aimed to characterize the hepatic gene expression in spontaneously hypertensive rats (SHR) at different ages. Blood pressure in SHR was determined by tail-cuff method at one and three months of age. Hepatic RNA was isolated and gene expression was compared using microarrays. Comparison between SHR and normotensive rats revealed significant variation in gene expression: 98 genes were upregulated and 122 were downregulated in SHR;while 88 genes were upregulated and 139 genes were downregulated in age-matched normotensive rats. Furthermore, within the SHR group, 110 genes were found to be upregulated and 168 genes downregulated across different ages. Analyses via the Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathways revealed that several genes are potentially implicated in both, hypertension and metabolic syndrome. The results suggest that SHR display variations in gene expression due to aging, and when compared to normotensive rats. These variations could contribute to the development of hypertension and metabolic syndrome. Microarray studies involving older rats are necessary to further validate these findings.