Journal of Cardiovascular Translational Research

The aim of this study was to investigate the effect of exercise on extracellular vesicles (EVs) in patients with metabolic dysfunction. The literatures were searched until Apr 28, 2022, and 16 studies that met inclusion criteria were included in this review. The results showed that the concentrations of platelet-derived extracellular vesicles (PEVs) and endothelial cell-derived extracellular vesicles (EEVs) decreased after long-term exercise, especially for CD62E+ EEVs and CD105+ EEVs. Simultaneously, exercise improved the concentration of clinical evaluation indicators of metabolic diseases, and the changes in these indicators were positively correlated with the changes of EEVs and PEVs. The concentration of skeletal muscle-derived extracellular vesicles (SkEVs) increased after a single bout of exercise. The aforementioned results indicated that long-term exercise might improve endothelial function and hypercoagulability in patients with metabolic dysfunction. The changes in concentrations of EVs could assist in assessing effect of exercise on patients with metabolic dysfunction.

Under normal conditions, autophagy maintains cardiomyocyte health and integrity through turnover of organelles. During stress, oxygen and nutrient deprivation, or microbial infection, autophagy prolongs cardiomyocyte survival. Sex differences in induction of cell death may to some extent explain the disparity between the sexes in many human diseases. However, sex differences in gene expression, which regulate cell death and autophagy, were so far not taken in consideration to explain the sex bias of viral myocarditis. Coxsackievirus B3 (CVB3)-induced myocarditis is a sex-biased disease, with females being substantially less susceptible than males and sex hormones largely determine this bias. CVB3 was shown to induce and subvert the autophagosome for its optimal viral RNA replication. Gene expression analysis on mouse and human, healthy and CVB3-infected, cardiac samples of both sexes, suggests sex differences in autophagy-related gene expression. This review discusses the aspects of sex bias in autophagy induction in cardiomyocytes.

Cardiovascular disease (CVD) is one of the leading causes of death worldwide. CVD includes coronary artery diseases such as angina, myocardial infarction, and stroke. “Lipid hypothesis” which is also known as the cholesterol hypothesis proposes the linkage of plasma cholesterol level with the risk of developing CVD. Conventional management involves the use of statins to reduce the serum cholesterol levels as means for CVD prevention or treatment. The regulation of serum cholesterol levels can potentially be regulated with biological interventions like monoclonal antibodies. Phage display is a powerful tool for the development of therapeutic antibodies with successes over the recent decade. Although mainly for oncology, the application of monoclonal antibodies as immunotherapeutic agents could potentially be expanded to CVD. This review focuses on the concept of phage display for antibody development and discusses the potential target antigens that could potentially be beneficial for serum cholesterol management.

The interactions and hemodynamic impact of transcatheter percutaneous mitral valve repair (TMR) have not yet been investigated in patients undergoing left ventricular assist device (LVAD) implantation, but hemodynamic adverse effects are feared in the combination of TMR and LVAD for altered mitral valve flow. This study investigated the hemodynamic interplay in combination of TMR and LVAD in 119 patients, and propensity score match analysis revealed no difference in both perioperative mortality and 2-year follow-up survival (p = 0.84). Nonetheless, postoperatively mean pulmonary arterial pressure, pulmonary capillary wedge pressure, and cardiac index improved, and multivariable cox regression analysis at 2 years identified preoperative total bilirubin and temporary right ventricular mechanical circulatory support as independent risk factors for all-cause mortality but not TMR. Prior TMR has no impact on mortality or cardiovascular complications in patients with LVAD.

Our aim was to analyse the associations between carotid plaque burden (CPB), cardiovascular risk factors (CVRF), and surrogate markers of CV risk in subjects with metabolic syndrome (MetS). We consecutively included 75 asymptomatic outpatients with MetS components, <60 years old and non-smokers. We determined the presence of CVRF, left ventricular hypertrophy (LVH), carotid intima-media thickness (cIMT), albumin-creatinine ratio (ACR), coronary artery calcium score (CACS) and CPB by 3-dimensional vascular ultrasound (3DVUS) for comparison. A total of 50 (67%) subjects had MetS defined by harmonized criteria. A CPB >0 mm3 and a CACS >0 AU were the risk biomarkers most frequently observed (72% and 77%, respectively), followed by LVH (40%). CPB and CACS revealed association with cardiovascular risk (r = 0.308; p = 0.032 and r = 0.601 p < 0.01, respectively), and CPB also showed association with the burden of CVRF (r = 0.349; p = 0.014). CPB by 3DVUS was a prevalent CV risk marker, directly associated with CVRF and cardiovascular risk in MetS subjects.

Personalized medicine is defined as individualized treatment based on the individual’s genetic variants. Such treatment has the potential to enable pharmacogenetics, such as the prevention of 100,000 deaths per year in the USA because of adverse drug reactions or specify treatment in heart failure such at the beta 1 adrenergic receptor polymorphisms. It is claimed that coronary artery disease (CAD) is at least 50% because of genetic predisposition. Identification of the genes predisposing to CAD would greatly facilitate prevention, early treatment, and more specific therapies. The arrival of the multimillion single nucleotide polymorphism (SNP) array provides the high throughput genotyping required to perform genome-wide Association (GWA) studies. These studies require markers (SNPs) at intervals of 6,000 bp and sample size of several thousands. Platforms are available to genotype and process millions of genotypes per day. The GWA performed by the Ottawa Heart Genomic Study identified the first deoxyribonucleic acid region (9p21) predisposing to CAD after replication in six independent populations totaling 23,000. This was subsequently confirmed in several independent studies totally more than 45,000 individuals. The region confers a risk for CAD independent of known risk factors. 9p21 occurs in heterozygous form in 40 to 50% of Caucasians with increased risk of 15 to 20% and in homozygous form in 25% of Caucasians with increased risk of 40%. Identification of the genes predisposing to CAD is a prerequisite for personalized care of these patients. It is anticipated that most of the genes predisposing to CAD will be identified in the next 5 to 8 years. The 9p21, in addition to conferring increased risk, provides the bonus of being independent of known risk factors. Thus, 9p21 is likely to provide the impetus and nidus for a major research effort over the next few years. It has the potential to not only provide for early genetic screening but also as a target for novel therapy.

Several prior studies have highlighted the promise of mesenchymal stem cells (MSCs) as tools for treating myocardial infarction (MI) patients. While MSCs were initially thought to mediate post-MI repair through differentiation and replacement of injured cells, they are now thought to function by releasing exosomes carrying important cargos which can prevent apoptosis and facilitate revascularization in the context of MI. Herein, we comprehensively survey prior preclinical studies examining MSC-derived exosomes (MSC-Exos) utility for the repair of MI-related tissue injury. In total, 24 relevant studies were identified in the PubMed, Web of Science, Embase, and Cochrane Library databases as per the PRISMA guidelines. In most studies, exosome-treated rodents exhibited improved cardiac function and angiogenesis together with decreased apoptotic cell death. MSC-Exos thus offer beneficial therapeutic efficacy when treating MI injury. However, further work will be necessary to standardize experimental preclinical models and to validate these results. This systematic review provides a comprehensive overview of previous preclinical studies on the utility of exosomes derived from mesenchymal stem cells (MSCs) in the repair of myocardial infarction (MI) injury.

Recent advances in image-based modeling and computational fluid dynamics permit the calculation of coronary artery pressure and flow from typically acquired coronary computed tomography (CT) scans. Computed fractional flow reserve is the ratio of mean coronary artery pressure divided by mean aortic pressure under conditions of simulated maximal coronary hyperemia, thus providing a noninvasive estimate of fractional flow reserve (FFRCT) at every point in the coronary tree. Prospective multicenter clinical trials have shown that computed FFRCT improves diagnostic accuracy and discrimination compared to CT stenosis alone for the diagnosis of hemodynamically significant coronary artery disease (CAD), when compared to invasive FFR as the reference gold standard. This promising new technology provides a combined anatomic and physiologic assessment of CAD in a single noninvasive test that can help select patients for invasive angiography and revascularization or best medical therapy. Further evaluation of the clinical effectiveness and economic implications of noninvasive FFRCT are now being explored.

There is no consensus regarding the benefit of antihypertensive therapy on left ventricular structure and function. The most of studies investigated the effect of therapy on left ventricular hypertrophy, less studies were focused on left ventricular diastolic dysfunction and the minority on left ventricular mechanics. The majority of investigations showed positive effect of antihypertensive therapy on regression of left ventricular remodeling. Nevertheless, it is very difficult to distinguish the effect of antihypertensive medication from the effect of blood pressure reduction on left ventricular improvement. The other important issue in these studies is difficulty to distinguish the effect of left ventricular hypertrophy regression from the effect of antihypertensive medications on left ventricular diastolic function and mechanics. The novel findings suggest that the cascade of left ventricular remodeling in hypertensive heart disease begins with mechanical changes, continuous with diastolic dysfunction, and ends with left ventricular hypertrophy. This is very important paradigm because it enables early and timely diagnosis of subclinical left ventricular damage in hypertensive patients and should provide rapid detection of left ventricular function improvement during antihypertensive therapy.

Monocytes are central mediators in the development of atherosclerotic plaques. They circulate in blood and eventually migrate into tissue including the vessel wall where they give rise to macrophages and dendritic cells. The existence of monocyte subsets with distinct roles in homeostasis and inflammation suggests specialization of function. These subsets are identified based on expression of the CD14 and CD16 markers. Routinely applicable protocols remain elusive, however. Here, we present an optimized four-color flow cytometry protocol for analysis of human blood monocyte subsets using a specific PE-Cy5–conjugated monoclonal antibody (mAb) to HLA-DR, a PE-Cy7-conjugated mAb to CD14, a FITC-conjugated mAb to CD16, and PE-conjugated mAbs to additional markers relevant to monocyte function. Classical CD14+CD16− monocytes (here termed “Mo1” subset) expressed high CCR2, CD36, CD64, and CD62L, but low CX3CR1, whereas “nonclassical” CD14loCD16+ monocytes (Mo3) essentially showed the inverse expression pattern. CD14+CD16+ monocytes (Mo2) expressed high HLA-DR, CD36, and CD64. In patients with stable coronary artery disease (n = 13), classical monocytes were decreased, whereas “nonclassical” monocytes were increased 90% compared with healthy subjects with angiographically normal coronary arteries (n = 14). Classical monocytes from CAD patients expressed higher CX3CR1 and CCR2 than controls. Thus, stable CAD is associated with expansion of the nonclassical monocyte subset and increased expression of inflammatory markers on monocytes. Flow cytometric analysis of monocyte subsets and marker expression may provide valuable information on vascular inflammation. This may translate into the identification of monocyte subsets as selective therapeutic targets, thus avoiding adverse events associated with indiscriminate monocyte inhibition.