Calcitriol Suppressed Isoproterenol-induced Proliferation of Cardiac Fibroblasts via Integrinβ3/FAK/Akt Pathway

Objective Cardiac fibroblasts(CFs)proliferation and extracellular matrix deposition are important features of cardiac fibrosis.Various studies have indicated that vitamin D displays an anti-fibrotic property in chronic heart diseases.This study explored the role of vitamin D in the growth of CFs via an integrin signaling pathway.Methods MTT and 5-ethynyl-2′-deoxyuridine assays were performed to determine cell viability.Western blotting was performed to detect the expression of proliferating cell nuclear antigen(PCNA)and integrin signaling pathway.The fibronectin was observed by ELISA.Immunohistochemical staining was employed to evaluate the expression of integrinβ3.Results The PCNA expression in the CFs was enhanced after isoproterenol(ISO)stimulation accompanied by an elevated expression of integrin beta-3(β3).The blockade of the integrinβ3 with a specific integrinβ3 antibody reduced the PCNA expression induced by the ISO.Decreasing the integrinβ3 by siRNA reduced the ISO-triggered phosphorylation of FAK and Akt.Both the FAK inhibitor and Akt inhibitor suppressed the PCNA expression induced by the ISO in the CFs.Calcitriol(CAL),an active form of vitamin D,attenuated the ISO-induced CFs proliferation by downregulating the integrinβ3 expression,and phosphorylation of FAK and Akt.Moreover,CAL reduced the increased levels of fibronectin and hydroxyproline in the CFs culture medium triggered by the ISO.The administration of calcitriol decreased the integrinβ3 expression in the ISO-induced myocardial injury model.Conclusion These findings revealed a novel role for CAL in suppressing the CFs growth by the downregulation of the integrinβ3/FAK/Akt pathway.

Tenascin C upregulates interleukin-6 expression in human cardiac myofibroblasts via toll-like receptor 4

AIM:To investigate the effect of Tenascin C(TNC)on the expression of pro-inflammatory cytokines and matrixmetalloproteinases in human cardiac myofibroblasts(CMF).METHODS:CMF were isolated and cultured from patients undergoing coronary artery bypass grafting.Cultured cells were treated with either TNC(0.1μmol/L,24 h)or a recombinant protein corresponding to different domains of the TNC protein;fibrinogen-like globe(FBG)and fibronectin typeⅢ-like repeats(TNⅢ5-7)(both 1μmol/L,24 h).The expression of the proinflammatory cytokines;interleukin(IL)-6,IL-1β,TNFαand the matrix metalloproteinases;MMPs(MMP1,2,3,9,10,MT1-MMP)was assessed using real time RT-PCR and western blot analysis.RESULTS:TNC increased both IL-6 and MMP3(P<0.01)mR NA levels in cultured human CMF but had no significant effect on the other markers studied.The increase in IL-6 mR NA expression was mirrored by an increase in protein secretion as assessed by enzymelinked immunosorbant assay(P<0.01).Treating CMF with the recombinant protein FBG increased IL-6mR NA and protein(P<0.01)whereas the recombinant protein TNⅢ5-7 had no effect.Neither FBG nor TNⅢ5-7 had any significant effect on MMP3 expression.The expression of toll-like receptor 4(TLR4)in human CMF was confirmed by real time RT-PCR,western blot and immunohistochemistry.Pre-incubation of cells with TLR4neutralising antisera attenuated the effect of both TNC and FBG on IL-6 mR NA and protein expression.CONCLUSION:TNC up-regulates IL-6 expression in human CMF,an effect mediated through the FBG domain of TNC and via the TLR4 receptor.

Effects of Paeonol on Expression of Type Ⅰ and Type Ⅲ Collagen of High Glucose Induced Proliferation of Cardiac Fibroblasts

[Objectives]To explore the effects of paeonol on the inhibition of myocardial fibrosis in high glucose induced cardiac fibroblasts(CFs).[Methods]Differential adherence method was used to culture the primary CFs of neonatal rats(passage culture);CCK-8 method was used to detect the cell proliferation;MTT assay was used to screen the safe concentration of paeonol;the 2 nd to 3 rd generation CFs were randomly divided into normal group(5.5 mmol/L,expressed in C),high glucose group(30 mmol/L,expressed in HG),paeonol low dose group(Pae-L,17.5 mg/L),and medium dose paeonol group(Pae-M,35 mg/L),paeonol high dose group(Pae-H,70 mg/L);Western Blot method was used to detect the expression of Col-I and Col-III protein.[Results]The extraction of CFs from primary neonatal rats was successful;high glucose(30 mmol/L)induction had a significant proliferation effect on CFs;compared with the normal group,the expressions of COI-I and Col-III protein were increased in the high glucose group(P<0.05);compared with the high glucose group,the expression of COI-I protein was decreased in each treatment group(P<0.05,P<0.01),and the decrease was most significant in the high dose group(P<0.01);the expression of COI-III in the high dose group was decreased and it was statistically significant(P<0.05).[Conclusions]Paeonol significantly inhibited the proliferation of high glucose induced CFs in neonatal rats.This experiment is intended to provide a new experimental basis for the prevention and treatment of diabetic cardiomyopathy(DCM).

Effect of aldosterone on the proliferation of rat cardiac fibroblasts

Objective:A cell model of cardiac fibroblasts proliferation induced by aldosterone was established to observe the effect of aldosterone on the proliferation of rat cardiac fibroblasts.Methods:Primary cardiac fibroblasts were cultured by trypsin digestion method and differential adhesion method,primary cardiac fibroblasts were sub-cultured by conventional digestion method,and the immunocytochemical assay was used to identify cardiac fibroblasts.The second-generation cardiac fibroblasts were randomly divided into five groups:standard control group,10-9 mol/L aldosterone(ALD1)group,10-8 mol/L aldosterone(ALD2)group,10-7 mol/L aldosterone(ALD3)group,and 10-6 mol/L aldosterone(ALD4)group.The viability of fibroblast cells in each group was detected by the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method.Results:Vimentin staining assay showed that the cultured cells staining positive,and the purity of cultured mouse cardiac fibroblasts was 95%.The results of methyl thiazolyl tetrazolium showed that compared with the control group,the low concentration of aldosterone(10-9 mol/L)had no significant effect on the proliferation of normal cardiac fibroblasts.With the increase in the intensity of(10-8–10-6)mol/L,aldosterone could significantly promote the proliferation of cardiac fibroblasts.Moreover,there was no significant difference in absorbance value between the aldosterone group(10-6 mol/L)and the aldosterone group(10-7 mol/L)(P>0.05).The highest concentration of aldosterone group 10-7 mol/L promoted the proliferation of cardiac the optimum concentration was 10-7 mol/L.Conclusion:Aldosterone can promote the spread of cardiac fibroblasts in a specific concentration range.

Cardiac arrest, stony heart, and cardiopulmonary resuscitation: An updated revisit

The post-resuscitation period is recognized as the main predictor of cardiopul-monary resuscitation(CPR)outcomes.The first description of post-resuscitation syndrome and stony heart was published over 50 years ago.Major manifestations may include but are not limited to,persistent precipitating pathology,systemic ischemia/reperfusion response,post-cardiac arrest brain injury,and finally,post-cardiac arrest myocardial dysfunction(PAMD)after successful resuscitation.Why do some patients initially survive successful resuscitation,and others do not?Also,why does the myocardium response vary after resuscitation?These ques-tions have kept scientists busy for several decades since the first successful resuscitation was described.By modifying the conventional modalities of resu-scitation together with new promising agents,rescuers will be able to salvage the jeopardized post-resuscitation myocardium and prevent its progression to a dismal,stony heart.Community awareness and staff education are crucial for shortening the resuscitation time and improving short-and long-term outcomes.Awareness of these components before and early after the restoration of circulation will enhance the resuscitation outcomes.This review extensively addresses the underlying pathophysiology,management,and outcomes of post-resuscitation syndrome.The pattern,management,and outcome of PAMD and post-cardiac arrest shock are different based on many factors,including in-hospital cardiac arrest vs out-of-hospital cardiac arrest(OHCA),witnessed vs unwitnessed cardiac arrest,the underlying cause of arrest,the duration,and protocol used for CPR.Although restoring spontaneous circulation is a vital sign,it should not be the end of the game or lone primary outcome;it calls for better understanding and aggressive multi-disciplinary interventions and care.The development of stony heart post-CPR and OHCA remain the main challenges in emergency and critical care medicine.

Serelaxin inhibits inflammatory response induced by LPS in cardiac fibroblasts via activating PPAR-Y and suppressing NF-κB signaling pathway

Various models of cardiovascular disease that have been used to demonstrate the anti-fibrotic effects of serelaxin.However,whether anti-fibrotic effects of serelaxin are achieved by inhibiting inflammatory responsere have not been uncovered.Our study aimed to investigate the role of serelaxin in lipopolysaccharide(LPS)-induced inflammation of cardiac fibroblasts(CFs)and clarify the potential mechanisms.Cardiac fibroblasts(CFs)were isolated from the hearts of 3 days neonatal rats.Effects of serelaxin on inhibiting in fAammatory response after induction with LPS were examined.Cell viability was determined by cell-counting kit-8.The inflammatory cytokines secretion levels of IL-1,IL-6 and TNF-α,along with IL-10 were measured by enzyme-linked immunosorbent assay(ELISA)respectively.

Effect of cardiac rehabilitation care after coronary intervention on cardiac function recovery and negative mood in patients with myocardial infarction

BACKGROUND Cardiovascular disease,particularly myocardial infarction(MI)profound impact on patients'quality of life and places a substantial burden on the healthcare and economy systems.Developments in medical technology have led to the emer-gence of coronary intervention as an essential method for treating MI.AIM To assess the effects of cardiac rehabilitation care on cardiac function recovery and negative emotions in MI after coronary intervention.METHODS This study included a total of 180 patients with MI during the period from June 2022 to July 2023.Selected patients were divided into two groups:An observation group,which receiving cardiac rehabilitation care;a control group,which re-ceiving conventional care.By comparing multiple observation indicators such as cardiac function indicators,blood pressure,exercise tolerance,occurrence of adverse cardiac events,and negative emotion scores between the two groups of patients.All the data were analyzed and compared between two groups.RESULTS There were 44 males and 46 females in the observation group with an average age of 36.26±9.88 yr;there were 43 males and 47 females in the control group,with an average age of 40.87±10.5 yr.After receiving the appropriate postoperative nursing measures,the results of the observation group showed significant improvement in several indicators compared with the control group.Indicators of cardiac function,such as left ventricular end-diastolic internal diameter and left ventricular ejection fraction were significantly better in the observation group than in the control group(P<0.05).Exercise endurance assessment showed that the 6-minute walking test distance was significantly increased in the patients of the observation group(P<0.01).In addition,the incidence of adverse cardiac events was significantly lower in the observation group,and negative mood scores were significantly reduced(P<0.05).CONCLUSION Cardiac rehabilitation care after coronary intervention has a significant positive impact on functional recovery.This emphasizes the importance of cardiac rehabilitation care to improve patient recovery.

Overall approaches to cardiac tumors:Still an unsolved enigma?

Cardiac tumors are neoplasms involving heart structures at any level,meaning the myocardium,valves,and cardiac chambers.When considering cardiac masses,it is not uncommon for surgeons to be surprised when they diagnose one.The real incidence of this complex group of diseases has been explored only after cardiac diagnostic tools became more appropriate.Despite differential diagnosis being relevant,surgical indication is usually requested for all malignant cardiac tumors and also for many types of benign tumors.The development of cardiac imaging techniques,therefore,has been the key point for a better understanding of the history of cardiac tumors and especially of the relevance of surgical indication in such conditions.Systematic and combined applications of echocardiography,cardiac computed tomography and magnetic resonance allow in the majority of case a clear definition of the nature of a newly discovered cardiac mass.The presence of a Li-Fraumeni syndrome seems to be the trigger aspect in accelerating the propensity of developing a cardiac tumor.Despite the revolutionary usefulness of the cardiac imaging techniques available,it is still considered a hazard to diagnose a malignant cardiac mass just with radiological imaging;the mainstay of the final diagnosis stands in surgical excision of the mass and histopathological report.

Cardiac rehabilitation after cardiac surgery:An important underutilized treatment strategy

Physical inactivity remains in high levels after cardiac surgery,reaching up to 50%.Patients present a significant loss of functional capacity,with prominent muscle weakness after cardiac surgery due to anesthesia,surgical incision,duration of cardiopulmonary bypass,and mechanical ventilation that affects their quality of life.These complications,along with pulmonary complications after surgery,lead to extended intensive care unit(ICU)and hospital length of stay and significant mortality rates.Despite the well-known beneficial effects of cardiac rehabilitation,this treatment strategy still remains broadly underutilized in patients after cardiac surgery.Prehabilitation and ICU early mobilization have been both showed to be valid methods to improve exercise tolerance and muscle strength.Early mobilization should be adjusted to each patient’s functional capacity with progressive exercise training,from passive mobilization to more active range of motion and resistance exercises.Cardiopulmonary exercise testing remains the gold standard for exercise capacity assessment and optimal prescription of aerobic exercise intensity.During the last decade,recent advances in healthcare technology have changed cardiac rehabilitation perspectives,leading to the future of cardiac rehabilitation.By incorporating artificial intelligence,simulation,telemedicine and virtual cardiac rehabilitation,cardiac surgery patients may improve adherence and compliance,targeting to reduced hospital readmissions and decreased healthcare costs.

Effects of systematic cardiac rehabilitation training in elderly patients with unstable angina following cardiac stent implantation

BACKGROUND Coronary stent implantation is usually used to treat unstable angina to alleviate stenosis or occlusion,promoting blood flow restoration and alleviating symptoms such as myocardial ischemia.And postoperative cardiac rehabilitation is essential for enhancing recovery and prognosis.Nevertheless,conventional rehabilitation lacks specificity,particularly for elderly patients with multiple comorbidities and poor compliance,rendering it less effective.AIM To investigate the effects of systematic cardiac rehabilitation training in elderly patients with unstable angina following coronary stenting intervention.METHODS A retrospective enrollment was conducted comprising fifty-four elderly patients with unstable angina pectoris who underwent systematic cardiac rehabilitation training after receiving coronary intervention as the rehabilitation group,while fifty-three elderly patients who received basic nursing and rehabilitation guidance measures after coronary intervention were assigned to the control group.Differences in Seattle Angina Questionnaire scores,survival quality(SF-36)scores,cardiopulmonary exercise function assessment index,echocardiographic cardiac function index,and adverse cardiovascular events were compared between the two groups.RESULTS After intervention,the rehabilitation group observed greater VO2 Max,maximum metabolic equivalent,eft ventricular ejection fraction,left ventricular end-diastolic diameter and smaller left ventricular end-systolic diameter.And the rehabilitation group observed greater scores of physical activity limitation,stable angina pectoris,treatment satisfaction,and SF-36 score.The incidence of adverse cardiovascular events in the two groups,showed no significant difference.CONCLUSION Systematic cardiac rehabilitation following coronary stenting in elderly patients with unstable angina pectoris can enhance cardiac function recovery,consequently enhancing both quality of life and cardiopulmonary exercise tolerance.

Hypoxia-preconditioned bone marrow-derived mesenchymal stem cells protect neurons from cardiac arrest-induced pyroptosis

Cardiac arrest can lead to severe neurological impairment as a result of inflammation,mitochondrial dysfunction,and post-cardiopulmonary resuscitation neurological damage.Hypoxic preconditioning has been shown to improve migration and survival of bone marrow–derived mesenchymal stem cells and reduce pyroptosis after cardiac arrest,but the specific mechanisms by which hypoxia-preconditioned bone marrow–derived mesenchymal stem cells protect against brain injury after cardiac arrest are unknown.To this end,we established an in vitro co-culture model of bone marrow–derived mesenchymal stem cells and oxygen–glucose deprived primary neurons and found that hypoxic preconditioning enhanced the protective effect of bone marrow stromal stem cells against neuronal pyroptosis,possibly through inhibition of the MAPK and nuclear factor κB pathways.Subsequently,we transplanted hypoxia-preconditioned bone marrow–derived mesenchymal stem cells into the lateral ventricle after the return of spontaneous circulation in an 8-minute cardiac arrest rat model induced by asphyxia.The results showed that hypoxia-preconditioned bone marrow–derived mesenchymal stem cells significantly reduced cardiac arrest–induced neuronal pyroptosis,oxidative stress,and mitochondrial damage,whereas knockdown of the liver isoform of phosphofructokinase in bone marrow–derived mesenchymal stem cells inhibited these effects.To conclude,hypoxia-preconditioned bone marrow–derived mesenchymal stem cells offer a promising therapeutic approach for neuronal injury following cardiac arrest,and their beneficial effects are potentially associated with increased expression of the liver isoform of phosphofructokinase following hypoxic preconditioning.

Effects of glucose and aldosterone on the proliferation of cardiac fibroblasts

在老鼠的增长上调查葡萄糖和醛固酮的效果的目的心脏的成纤维细胞。方法新生的 SD 老鼠心脏的成纤维细胞(Cfs ) 被微分附件技术分开。Cfs 在不同 D 葡萄糖集中被孵化 24 个小时，与或没有醛固酮。DNA 合成和 Cfs 的新陈代谢的活动分别地与 Brdu 加入和 WST-1 ELISA 同时被测量。在高集中(15 和 25 mmol/L ) 的结果葡萄糖显著地增加了 Cfs 的增长，与在低集中的葡萄糖相比(5.6 mmol/L， .PO.01 ) ，当没有差别在在二高葡萄糖之间的 Cfs 增长上被显示出时，集中组织。没有醛固酮，到低葡萄糖的媒介的醛固酮(10-7 mmol/L ) 的增加与那些相比导致了重要增长(WST-1， P < 0.01；Brdu， P=0.019 ) 。然而，当在高葡萄糖媒介孵化了时，为 Cfs 增长的醛固酮的刺激效果消失了(P > 0.05 ) 。进一步的分析建议醛固酮在 Cfs DNA 合成(P=0.012 ) 上有重要相互作用。葡萄糖和醛固酮能刺激有教养的 Cfs 的增长的结论。在高葡萄糖集中，为 Cfs 增长的 stimulatory 效果可以被掩盖。

Interleukin-22 regulating fibrosis on mouse cardiac fibroblasts through STAT3 signaling pathway

Objective:To observe the effects of interleukin-22(IL-22)on the expression of type Ⅲ collagen,cytokines,growth factors and chemokines in mouse cardiac fibroblasts in vitro.Methods:Mouse cardiac fibroblasts were treated with0μg/L(control),1μg/L(low concentration)and 100μg/L(high concentration)IL-22,respectively.In addition,cells treated with 100μmol/L static(an STAT3 pathway inhibitor)and 100μg/L IL-22 was defined as the block group.After treatment for 48 hours,the mRNA level of collagen type Ⅲ A1(Col3-A1),matrix metalloproteinase-1(Timp-1),IL-22receptor(IL-22R),interleukin 10-related T cellderived inducible factor beta(Iltifb),fibroblast growth factor1(Fgf1)and C-C motif chemokine ligand 4(Ccl4)were determined by RT-PCR.The expression of Col3-A1 in cardiac fibroblasts was also semi-quantified by immunofluorescence.Results:Expression of Col3-A1 decreased in the low and high concentration groups,but significantly increased in the block group(all P <0.05).The expression of Timp-1increased in the low,high concentration and block groups compared with that in the control group,but it was significantly lower in the high concentration group than that in the low concentration group(P <0.05).The expression of IL-22 Rand Iltifb was significantly increased in the low,high concentration and block groups compared with that in the control group(P <0.05),but there was no statistical difference between the high concentration group and block group.The expression of Fgf1 and Ccl4 was significantly decreased in the low,high concentration and block groups compared with that in the control group(P <0.05),but there was no statistic difference between the high concentration group and block group as well.Conclusion:IL-22 effected on the expression of Col3-A1 and Timp-1,which was possibly through the JAK-STAT3 signaling pathway in mice cardiac fibroblasts.

The Combined Effect of Lumenato and Ceramide in the Protection of Collagen Damage Induced by Neutrophils in Normal Human Dermal Fibroblasts

Introduction: Collagen is the primary structural protein fibroblasts produce in the skin’s extracellular matrix. Infiltration of neutrophils into the epidermis and dermis by exposure to UV causes collagen damage and contributes to photoaging. Methods: To study the combined effect of Lumenato and ceramide in preventing collagen-1 damage induced by phagocytes, we used co-cultures of normal human dermal fibroblasts (fibroblasts) and activated human neutrophils. The present study aimed to determine the protective effect of the combination of Lumenato and ceramide on fibroblast collagen-1 damage induced by neutrophils. Results: Lumenato (in the range of 6.5 - 208 μg/ml) or ceramide (in the range of 0.1 - 50 μM) inhibited the production of superoxides and MPO by TNFα-stimulated neutrophils, as well as the production of NO by LPS-stimulated macrophages in a dose-dependent manner. The combinations of Lumenato and ceramide, in low concentrations, caused synergistic prevention of fibroblasts’ collagen-1 damage induced by TNFα-activated neutrophils, detected by fluorescence immunostaining and WB analysis. MPO activity in the supernatants of the co-cultures was also synergistically inhibited. Adding Lumenato or ceramide singly or in combinations in these low concentrations to the fibroblast cultures did not affect the expression of collagen-1. The combinations of Lumenato or ceramide in these concentrations also caused a synergistic inhibition of NO production by activated macrophages. Conclusions: The results suggest that combining low concentrations of Lumenato and ceramide results in synergistic protection against fibroblasts’ collagen-1 damage induced by neutrophils, thus indicating their possible potential for enhanced skin health.

A contradictory phenomenon of thicken pericardium and cardiac compression without inferior vena cava dilation:sign of IVC escape

A 77-year-old female presented with shortness of breath and tightness of chest was admitted.Her past medical history included hypertension and she has been taking nifedipine regularly.Two years before,she was diagnosed with pericardial effusion(Figure 1)and had pericardiocentesis drainage.On physical examination,her blood pressure was 151/100 mm-Hg and her pulse rate was 91 beats/min.

Total suprarenal aortic occlusion with cardiac disease: a case series of three cases

Acute aortic occlusion(AAO)has been very rarely reported in the literature and is a potentially life-threatening emergency.[1-5]AAO mostly occurs in cardiac disease patients,[1-4,6,7]and leads to cardiac complications.[1,2,5,6]Suprarenal aortic occlusion(SAO)is a very rare type of AAO,and infrarenal aortic occlusion(IAO)accounts for 75.8%-97.8%.[1,3,5-7]SAO is different from IAO in some clinical manifestations,treatment strategies,and prognoses.[3,6-8]SAO with cardiac disease will make the condition more complex and could easily cause a delay in diagnosis and portend worse outcomes with amputation and mortality rates.[1,3,6]Early and fast diagnosis and positive revascularization treatment are necessary to prevent cases from becoming fatal.[1-3]Herein,we present a case series of SAO with cardiac disease.

The association between C-reactive protein to albumin ratio and 6-month neurological outcome in patients with in-hospital cardiac arrest

The global incidence rates of in-hospital cardiac arrest(IHCA)range from1.2 to 9.0 per1,000 hospitalized patients,as per the National Cardiac Arrest Database.[1] While IHCAs tend to exhibit superior 30-day survival rates relative to out-of-hospital cardiac arrests (OHCA) due to situational advantages,such as immediate access to medical personnel and treatments.

Utilization of biomarkers for the prognostic prediction of cardiac arrest survivors using a multi-modal approach

International guidelines for post-cardiac arrest care recommend using multi-modal strategies to avoid the withdrawal of life-sustaining therapy(WLST)in patients with the potential for neurological recovery.[1]However,a clear methodology for multi-modal approaches has yet to be developed.Neuron-specific enolase(NSE)is currently the only recommended biomarker,and the European Resuscitation Council(ERC)and the European SocietyofIntensiveCareMedicine(ESICM)have proposed a cutoff value of 60μg/L at 48 and/or 72 h after the return of spontaneous circulation(ROSC)as a multimodal prognostic tool for predicting poor neurological outcomes.

Cardiac infiltration of diffuse large B-cell lymphoma manifesting as sustained ventricular tachycardia:a case report

Cardiac tumors are rare.However,cardiac metastases can occur in up to 10%of patients with cancer.Among cardiac neoplasms,metastases are much more common than primary cardiac tumors.[1]Metastatic cardiac neoplasms most frequently metastasize from the respiratory system.