Human umbilical cord blood mesenchymal stem cells conditioned media inhibits hypoxia-induced apoptosis in H9c2 cells by activation of the survival protein Akt

This work aimed to study the beneficial role of human umbilical cord blood-derived mesenchymal stem cellconditioned medium(MSC-CM)in hypoxia-induced apoptosis in H9c2 cardiomyoblasts,in which the serine/heroine kinases(Akt)pathway would be involved.For this,CM was collected by culturing MSCs in serum-free DMEM medium for 24 h,and paracrine factors were analyzed by protein chip.H9c2 cells were divided into the following groups:control group,hypoxia group,MSC-CM intervention group(CM group),MSC-CM+Akt phosphorylation inhibitor(LY294002)group(LY group).Apoptosis of the H9c2 cells was tested with chromatin dye Hoechst 33342 and FITC-conjugated Annexin V apoptosis detection kit by flow cytometer after a hypoxia/serum deprivation(H/SD)for 24 h.The apoptosis-related proteins were evaluated by Western blot.MSC-CM displayed significantly elevated levels of growth factors,anti-inflammatory,and anti-apoptosis cytokines.On Hoechst 33342 apoptosis staining,the H9c2 cell morphology displayed a lower proportion of apoptosis in the CM group than those in the hypoxia group,while apoptosis was increased in LY group.Flow cytometer analysis revealed the apoptosis ratio in the CM group was lower than the hypoxia group(12.34±2.00%vs.21.73±2.58%,p<0.05),while the LY group was significantly higher(22.54±3.89%).Active caspase-3 expression was increased in hypoxia group than control group(p<0.05),but decreased in CM group(p<0.01).Umbilical cord blood-derived mesenchymal stem cell-conditioned media secrete multiple paracrine factors that are able to inhibit hypoxia-induced H9c2 cardiomyoblasts apoptosis,and in which the activation of Akt phosphorylation is involved to achieve the protective effect.

Exogenous dendritic cells aggravate atherosclerosis via P-selectin/PSGL-1 pathway

Studies have found that a large number of inflammatory cells,P-selectin,and mature dendritic cells(DCs)are expressed in the damaged and shoulder parts of atherosclerotic plaque,which demonstrates that P-selectin and mature DCs participate in the immune inflammatory response leading to the development of atherosclerosis.However,it is unclear how the above factors interact in this setting.In this study,we investigated the role of P-selectin and its receptor,P-selectin glycoprotein ligand(PSGL)-1 in atherosclerosis,with the finding that DC surface marker expression was consistently high in the P-selectin group while consistently low in the PGSL-1+DCs group,with CD40 and CD86 expressed by 3.84%and 2.05%for the latter.The highest expression of CD80,CD83,and MHC II was discovered in the DC group,at 7.49%,3.68%,and 8.98%,respectively.Results of this study are similar to those obtained previously by Ye et al.(2017),which showed larger atherosclerotic lesions in mice that received exogenous DCs,compared with those treated with PBS.In this study,the greatest level of atherosclerosis,fibrosis,and lipid deposition was also seen in mice that received exogenous DCs.

Global and national burden of atherosclerosis from 1990 to 2019:trend analysis based on the Global Burden of Disease Study 2019

Background:Atherosclerosis-related diseases represent significant health issues among adults globally.Despite their widespread impact,comprehensive data concerning the global and national burden and trends of these diseases remain sparse.Our objective is to examine the trends in the burden of atherosclerosis among adults from 1990 to 2019 at both global and national levels.Methods:We reported the average annual percentage changes(AAPCs)in prevalence,incidence,mortality,and disabilityadjusted life years(DALYs)of atherosclerosis-related diseases(ischemic heart disease[IHD],ischemic stroke,and peripheral arterial disease[PAD])at the global and national levels among individuals based on a trend analysis of the Global Burden of Diseases Study(GBD)2019.We further analyzed these global trends as a function of age,gender,and the social development index.We also used joinpoint regression analysis to identify the year with the most substantial changes in global trends.Results:Globally,the AAPC of IHD incidence rose from 1990 to 2019(0.20;95%confidence interval[CI],0.12-0.28),with substantial surges in 1995,2001,2005,2010,and 2017.Conversely,AAPC of IHD mortality rates exhibited a different trend until a rise in 2014.The AAPC of incidence rates of ischemic stroke and PAD also escalated during the same period,with respective 0.43(95%CI,0.39-0.48)and 0.13(95%CI,0.06-0.21).For ischemic stroke,both incidence and mortality soared in 2014,while PAD incidence declined in 1994 and 1998,then sharply climbed in 2016.Nationally,the Northern Mariana Islands experienced the steepest increase in IHD and PAD incidence and mortality between 1990 and 2019.China saw a significant rise in ischemic stroke incidence,whereas the highest mortality rate increase occurred in Timor-Leste.By sociodemographic index(SDI)quintile,low-middle-,middle-,and high-middle-SDI countries all showed upward trends in IHD,ischemic stroke,and PAD incidence.Simultaneously,IHD and ischemic stroke mortality rates,as well as DALYs,dropped in the low-,high-middle-,and high-SDI nations.However,PAD mortality rates and DALYs saw an uptick across all SDI quintiles.Regarding age demographics,a global decrease in the AAPC IHD incidence as noted in individuals above 55 years old,in contrast to an increase in the 20-55 age group during this period.AAPC of mortality rates for IHD,ischemic stroke,and PAD decreased across all ages.The AAPC showed an increase in IHD incidence in both genders.Conversely,IHD’s DALYs saw a reduction in both males and females.Ischemic stroke patterns mirrored these trends,whereas all measures for PAD exhibited growth for both sexes.Conclusions:From 1990 to 2019,there was an overall increasing trend in the global incidence of all three clinical manifestations of atherosclerosis.Between 1990 and 2019,both the mortality rate and DALYs for IHD and ischemic stroke declined across all age groups.Overall,the burden of atherosclerosis-related diseases has not significantly decreased and even shows signs of trending upward.These findings strongly suggest that despite some progress made,efforts to control atherosclerosis diseases globally need to be intensified.

Effect of complete percutaneous revascularization on improving long-term outcomes of patients with chronic total occlusion and multi-vessel disease

Background:Limited data are available on the comparison of clinical outcomes of complete vs.incomplete percutaneous coronary intervention(PCI)for patients with chronic total occlusion(CTO)and multi-vessel disease(MVD).The study aimed to compare their clinical outcomes.Methods:A total of 558 patients with CTO and MVD were divided into the optimal medical treatment(OMT)group(n=86),incomplete PCI group(n=327),and complete PCI group(n=145).Propensity score matching(PSM)was performed between the complete and incomplete PCI groups as sensitivity analysis.The primary outcome was defined as the occurrence of major adverse cardiovascular events(MACEs),and unstable angina was defined as the secondary outcome.Results:At a median follow-up of 21 months,there were statistical differences among the OMT,incomplete PCI,and complete PCI groups in the rates of MACEs(43.0%[37/86]vs.30.6%[100/327]vs.20.0%[29/145],respectively,P=0.016)and unstable angina(24.4%[21/86]vs.19.3%[63/327]vs.10.3%[15/145],respectively,P=0.010).Complete PCI was associated with lower MACE compared with OMT(adjusted hazard ratio[HR]=2.00;95%confidence interval[CI]=1.23–3.27;P=0.005)or incomplete PCI(adjusted HR=1.58;95%CI=1.04–2.39;P=0.031).Sensitivity analysis of PSM showed similar results to the above on the rates of MACEs between complete PCI and incomplete PCI groups(20.5%[25/122]vs.32.6%[62/190],respectively;adjusted HR=0.55;95%CI=0.32–0.96;P=0.035)and unstable angina(10.7%[13/122]vs.20.5%[39/190],respectively;adjusted HR=0.48;95%CI=0.24–0.99;P=0.046).Conclusions:For treatment of CTO and MVD,complete PCI reduced the long-term risk of MACEs and unstable angina,as compared with incomplete PCI and OMT.Complete PCI in both CTO and non-CTO lesions can potentially improve the prognosis of patients with CTO and MVD.

Association of blood pressure variability with target organ damage in older patients with essential hypertension

Background:Although multiple measures of blood pressure variability(BPV)have been proposed,whether they are better than mean blood pressure in predicting target organs is unclear.We aimed to determine the relationship between short term BPV and target organ injury.Methods:This study was a retrospective study,and 635 inpatients in the Department of Cardiology from 2015 to 2020 were selected.We divided participants into four groups on the basis of the quartiles of BPV.One-way analysis of variance was used to compare the differences between the groups,and linear regression was used to analyze the relationship between BPV and target organ damage.Results:The average age of 635 patients was 74.36±6.50 years old.Among them,354 of 627 patients had diminished renal function(56.5%),221of 604 patients had associated left ventricular hypertrophy(36.6%),and 227 of 231 patients had carotid plaque formation(98.3%).The baseline data indicated significant differences in fasting glucose,total cholesterol,low-density lipoprotein,creatinine,glomerular filtration rate,sex,calcium channel blocker use,and the rate of diminished renal function.Multiple linear regression analysis showed that BPV was negatively correlated with renal injury(creatinine:r=0.306,p<0.01;estimated glomerular filtration rate:r=0.058,p<0.01),and BPV is positively correlated with cardiac injury(r=0.083,p<0.01).Elevated BPV was not found to be associated with vascularinjury.Conclusion:Renal function decreases with increasing BPV and left ventricular mass increases with increasing BPV.

Focus on HFpEF in heart failure

There are so many of our patients who have had heart failure with preserved ejection fraction(HFpEF)and management really remains problematic.Approximately half of the patients with heart failure have preserved left ventrical(LV)systolic function and usually have some degree of diastolic dysfunction.Patients with reduced or preserved systolic function may have similar symptoms and it may be difficult to distinguish clinically between the two based on signs and symptoms.In developed countries,coronary artery disease(CAD)with resulting myocardial infarction and loss of functioning myocardium(ischemic cardiomyopathy)is the most common cause of systolic heart failure.Systemic hypertension remains an important cause of heart failure and,even more commonly in the United States,an exacerbating factor in patients with cardiac dysfunction because of other causes,such as CAD.Several processes may present with dilated or congestive cardiomyopathy,which is characterized by LV or biventricular dilation and generalized systolic dysfunction.Rare causes of dilated cardiomyopathy include infiltrative diseases(hemochromatosis,sarcoidosis,and amyloidosis),other infectious agents,metabolic disorders,cardiotoxins,and medication toxicity.Valvular heart diseases—particularly degenerative aortic stenosis and chronic aortic or mitral regurgitation—are frequent causes of heart failure.Persistent tachycardia,often related to atrial arrhythmias,can cause systolic dysfunction that may be reversible with controlling the rate.Diastolic cardiac dysfunction is associated with aging and related myocardial stiffening,as well as left ventricular hypertrophy(LVH),commonly resulting from hypertension.Conditions such as hypertrophic or restrictive cardiomyopathy,diabetes,and pericardial disease can produce the same clinical picture.Atrial fibrillation with or without rapid ventricular response may contribute to impaired left ventricular filling.

QRS score:A simple marker to quantify the extent of myocardial scarring in patients with chronic total arterial occlusion

Background:Chronic total occlusion(CTO)is a critical and unique subgroup of coronary lesions.This study aimed to investigate the correlation between the Selvester QRS score and late gadolinium enhancement cardiac magnetic resonance imaging(LGE-CMRI)in quantifying myocardial scarring to provide a simple and feasible method for treating CTO.Methods:The medical records of 134 patients with absolute CTO who underwent coronary angiography between May 1,2014 and December 30,2017 were retrospectively reviewed.All patients were grouped according to the CTO location(right coronary artery[RCA]CTO,left artery descending[LAD]CTO,left circumflex[LCX]CTO,and multivessel CTO groups).The degree of myocardial scarring was determined according to the Selvester QRS score and using the LGE-CMRI.All patients were followed up for at least 12 months.Results:Among the 62 CTO patients,55 had occlusion of a single vessel and seven had occlusion of multiple vessels,of which 27(43.55%)were in the RCA CTO group,16(25.81%)in the LAD CTO group,12(19.35%)in the LCX CTO group,and 7(11.29%)in the multivessel CTO group.The area under the receiver operating characteristic curve for the QRS score that was used to determine the degree of myocardial scarring was 0.806,with a sensitivity and specificity of 94.7%and 42.1%,respectively.The Selvester QRS score and LGE-CMRI measures of scar size were correlated in the RCA CTO,LCX CTO,and multivessel CTO groups(r=0.466,0.593,and 0.775,respectively).Conclusion:The Selvester QRS score was feasible for detecting myocardial scarring in patients with CTO.

Effects of long-term blood pressure variability on renal function in community population

High blood pressure is a significant contributor to premature mortality,resulting in nearly 10 million deaths and over 200 million disabilities worldwide.1 In recent years,hypertension treatment has shifted focus not only to average blood pressure but also to blood pressure variability(BPV),categorized into very short-term,short-term,and long-term BPV based on the time period of occurrence.2,3 Long-term BPV has emerged as clinically significant,with studies demonstrating its superiority in predicting long-term cardiovascular events,stroke,and mortality compared to short-term variability.Given its association with pre-renal function decline,reducing blood pressure fluctuations is imperative.