Hai-Yan Qian

Resveratrol in cardiovascular disease: what is known from current research?

Resveratrol is a well-known antioxidant that exists in grape skin/seed, red wine, and the root of Polygonum cuspidatum, a traditional Chinese and Japanese medicinal material. Studies have found that resveratrol has many interesting properties, including anti-carcinogenic properties, anti-microbial and antiviral effects, the ability to reverse dyslipidemia and obesity, the ability to attenuate hyperglycemia and hyperinsulinemia, and the ability to protect endothelial function. Heart failure is the final consequence of the majority of cardiovascular diseases, and resveratrol has been shown to directly attenuate heart contraction. The cardiovascular protective capacities of resveratrol are associated with multiple molecular targets and may lead to the development of novel therapeutic strategies for atherosclerosis, ischemia/reperfusion, metabolic syndrome, and heart failure. This article will mainly review recently published basic researches about the protective cardiovascular effects of resveratrol because these results may lead to the development of new clinical therapeutics in patients.

Intracoronary delivery of autologous bone marrow mononuclear cells radiolabeled by 18F‐fluoro‐deoxy‐glucose: Tissue distribution and impact on post‐infarct swine hearts

Intracoronary injection of the bone marrow‐derived mononuclear cells (MNCs) is emerging as a potentially novel therapy for ischemic heart failure. This study was aimed at assessing the efficacy of intracoronary MNC delivery in the myocardium. The in vivo distribution and myocardial homing of intracoronarily delivered MNCs in experimental Chinese swine with acute myocardial infarction (AMI) created by occlusion of left anterior descending (LAD) coronary artery for 90 min. MNCs radiolabeled with 18F‐fluoro‐deoxy‐glucose (18F‐FDG) were delivered using a coronary catheter into the infarct‐related coronary artery 1 week after AMI. Dual‐nuclide single photon emission computed tomography (SPECT) revealed that 1 h after cell infusion, 6.8 ± 1.8% of 18F‐FDG‐labeled MNCs occurred in the infarcted myocardium with the remaining activity found primarily in the liver and spleen. In the heart, MNCs were detected predominantly in the under‐perfused myocardium. The infused cells retained in the hearts at a rate highly correlated with the under‐perfused lesional sizes. Pathological examination further demonstrated that 6 weeks after infusion, compared to controls, the hearts receiving MNCs exhibited less fibrosis and inflammatory infiltrate, more viable tissue, and higher vascular density. Cardiac function was significantly improved in the MNC‐infused hearts. Thus, 18F‐FDG labeling and dual‐nuclide SPECT imaging is capable of monitoring in vivo distribution and homing of MNCs after intracoronary infusion. MNC coronary delivery may improve cardiac function and positive ventricular remodeling in the heart with AMI. J. Cell. Biochem. 102: 64–74, 2007.

Stem Cell Therapy Is a Promising Tool for Refractory Angina: A Meta-analysis of Randomized Controlled Trials

BACKGROUND So far, relatively few studies have addressed the use of stem cells to treat patients with refractory angina. Moreover, the results of current studies were discrepant. The objective of this meta-analysis was to evaluate the efficacy and safety of this treatment on a relatively large scale. METHODS Studies were identified through PubMed, CENTRAL, EMBASE, reviews, and reference lists of relevant papers. The weighted mean difference was calculated with random-effect models for net changes in exercise tolerance and angina frequency, and odds ratio (OR) with fixed-effect models for myocardial infarction (MI) and death. RESULTS Five randomized controlled trials, with a total of 381 patients, were included in the analysis. Compared with the controls, patients who received stem cell therapy had a significant improvement in exercise tolerance of 61.3 seconds (95% confidence interval [CI], 18.1-104.4; P = 0.005; I(2) = 58%); an obvious reduction in angina frequency of 7.3 episodes per week (95% CI, -13.4 to -1.2; P = 0.02; I(2) = 93%); and lower risk of MI, with an OR of 0.37 (95% CI, 0.14-0.95; P = 0.04; I(2) = 0%). No difference was detected for the risk of death (OR, 0.33; 95% CI, 0.08-1.39; P = 0.13; I(2) = 20%). CONCLUSIONS Stem cell therapy appears to be effective and safe in the management of patients with refractory angina. The findings need confirmation in larger-scale studies with longer follow-up.

Comparison of Clinical Features and Outcomes of Patients With Acute Myocardial Infarction Younger Than 35 Years With Those Older Than 65 Years

Purpose:The objective of this study was to analyze the clinical characteristics of patients younger than 35 years with acute myocardial infarction (AMI). Methods:A total of 117 patients younger than 35 years with AMI admitted to the hospital during the recent 10 years were chosen, and 355 patients older than 65 years with AMI served as a control group. The case history, clinical data, coronary angiography and prognosis of the patients were analyzed and compared. Results:Among the younger patients with AMI, men (96.6%) and those smoking cigarettes (66.7%) account for the majority. ST-segment elevation (69.2%) and anterior wall infarction (43.6%) were more prevalent in the younger patients than in the older patients. Compared with the older patients, the younger patients had a higher level of low-density lipoprotein cholesterol (2.93 ± 1.48 versus 2.35 ± 1.21, P = 0.0428) and higher left ventricular ejection fraction (59.82 ± 10.86 versus 48.31 ± 12.48, P = 0.0396). Coronary angiography data showed that most of the younger patients were characteristic of having single-vessel lesion (66.7%), left anterior descending artery lesion (69.3%) and coronary artery spasm more than the older patients (6.8% versus 0.56%, P = 0.0001). In addition, the in-hospital mortality, and the prognosis after 1 and 12 months in the younger patients were comparatively better. Conclusions:The main risk factors for young adults aged <35 years with AMI include cigarette smoking, hyperlipidemia and family history of coronary artery disease, and smoking cessation and lifestyle improvement are important considerations for the prevention of this disease in this population.

Attenuating Hypoxia-Induced Apoptosis and Autophagy of Mesenchymal Stem Cells: the Potential of Sitagliptin in Stem Cell-Based Therapy.

Background/Aims: Dipeptidyl peptidase-4 (DPP-4) inhibitors have pleiotropic effects on cardiovascular protection beyond the antidiabetic property. However, it remains unknown that the impact of one DPP-4 inhibitor sitagliptin on the survival of mesenchymal stem cells (MSCs) in hypoxia and serum deprivation (H/SD) environment. Methods: The apoptosis and autophagy of MSCs were analyzed in different concentrations of sitagliptin under H/SD condition. For later studies, we tested the relationship between anti-apoptotic and anti-autophagic effects of sitagliptin. The level of cell apoptosis was analyzed by Annexin V-FITC/PI staining, western blot of Bcl-2 and Bax proteins. Autophagy flux was assessed by multiple autophagy related proteins and substrates. Cell autophagy was identified by acridine orange staining, western blot of Beclin 1 and light chain 3 protein, and transmission electron microscopy. Results: We demonstrated that sitagliptin attenuated hypoxia-induced apoptosis and autophagy of MSCs. Furthermore, sitagliptin regulated cell autophagy by Bcl-2/ Beclin 1 pathway in H/SD condition. Conclusions: This study provides insight into the utility of the DPP-4 inhibitor sitagliptin for MSCs transplantation in the ischemic microenvironment that extends its antidiabetic property.

Role of endothelial lipase in atherosclerosis

Endothelial lipase, which is a newly identified member of the lipase family, plays an important role in high-density lipoprotein metabolism, which catalyzes the hydrolysis of high-density lipoprotein phospholipids and facilitates the clearance of high-density lipoprotein from the circulation. In addition, inflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1beta), upregulate endothelial lipase expression, and endothelial lipase also affects the expression of cytokines, which in turn play an important role in atherogenesis. Endothelial lipase expression has been associated with macrophages within human atherosclerotic lesions. However, an important challenge is to determine how endothelial lipase alters the progression of atherosclerosis. Although few data are available from human studies, it seems that plasma endothelial lipase levels in individuals with atherosclerosis might be higher than that measured in healthy individuals. Therefore, we believe that endothelial lipase might be a promising marker for atherosclerosis in clinical settings in the future.

Statins and stem cell modulation.

Stem cell-based therapy is a promising option for the treatment of ischemic heart diseases. As to a successful stem cell-based therapy, one of the most important issues is that the stable engraftment and survival of implanted stem cells in cardiac microenvironment. There are evidences suggest that pharmacological treatment devoted to regulate stem cell function might represent a potential new therapeutic strategy and are drawing nearer to becoming a part of treatment in clinical settings. Statins could exert cholesterol-independent or pleiotropic effects to cardiovascular system. Recent studies have shown that statins could modulate the biological characteristics and function of various stem cells, thus could be an effective method to facilitate stem cell therapy. This review will focus on statins and their modulation effects on various stem cells.

Stenting for left subclavian artery stenosis in patients scheduled for left internal mammary artery-coronary artery bypass grafting.

To evaluate the early and long‐term outcomes of stent placement for left subclavian artery stenosis (LSAS) in patients scheduled for left internal mammary artery‐coronary artery bypass grafting (LIMA‐CABG).

Heart-type Fatty Acid Binding Protein in the Assessment of Acute Pulmonary Embolism

Objective: To explore the predictive value of heart‐type fatty acid binding protein (H‐FABP) in the stratification and prognosis of patients with acute pulmonary embolism (APE). Methods: According to risk stratification, 69 patients with APE admitted into the emergency department within 24 hours after onset were divided into the following 3 groups: high‐risk group, moderate‐risk group and low‐risk group. H‐FABP‐ and cardiac troponin I (cTNI)‐positive rates of all groups were analyzed and compared, and the correlation between major adverse events (death, endotracheal intubation and cardiopulmonary resuscitation) and the cardiac markers (heart rate, arterial partial pressure of oxygen, right ventricular dimension, pulmonary arterial pressure, etc.) during the in‐hospital period were statistically analyzed. Then the prognosis (death, embolic pulmonary hypertension, right heart failure and recurrence of APE) at 6 months after onset of APE was followed‐up on and compared between groups. Results: The admission time of high‐risk group patients was earlier than non–high‐risk group (7.1 ± 2.9 versus 13.5 ± 6.7 versus 15.2 ± 10.7 hours, P = 0.001), had larger right ventricular dimension (33.1 ± 10.4 versus 26.7 ± 7.3 versus 20.5 ± 8.9 mm, P = 0.002) and higher pulmonary arterial pressure (45.8 ± 14.6 versus 29.4 ± 13.9 versus 23.1 ± 12.6 mm Hg, P = 0.001). The major adverse events during in‐hospital period, including death, endotracheal intubation and cardiopulmonary resuscitation, were more prevalent in the high‐risk group than those in the other 2 risk groups. Further analysis indicated that the positive rate of H‐FABP was remarkably higher than cTNI (52/69, 75.4% versus 28/69, 40.6%, P = 0.003). The H‐FABP (r = 0.881, P = 0.020) was significantly correlated to the major adverse events; however, this was not so regarding cTNI (r = 0.115, P = 0.059). At 6 months after onset of APE, the follow‐up data indicated that cTNI and H‐FABP were both significantly correlated with the major adverse events. Conclusions: The positive rate of H‐FABP was higher than cTNI during the 24 hours after the onset of APE. The H‐FABP was significantly correlated to the major adverse events during hospitalization and to the primary prognosis at 6 months after onset of APE.

Very small embryonic-like stem cells (VSELs)—A new promising candidate for use in cardiac regeneration

In recent years, stem cell-based therapy has been given increased attention in terms of its potential contribution to cardiac regeneration and repair, after acute myocardial infarction (AMI). The published studies have identified many kinds of stem cells with the ability to regenerate and repair damaged myocardium after AMI. These include embryonic stem cells (ESCs), mesenchymal stem cells (MSCs), multipotent adult progenitor cells, unrestricted somatic stem cells, etc. More recently, very small embryonic-like stem cells (VSELs) were identified from murine, as a population of very small CXCR4(+) Lin(-) CD45(-) cells and from human, as a population of very small CD34(+) CD133(+) CXCR4(+) Lin(-) CD45(-) cells. These cells exhibit beneficial effects on improving cardiac function and attenuating cardiac remodeling after AMI. However, the mechanisms underlying the benefits associated with VSELs therapy, in cardiac regeneration and repair, remain poorly understood. This review summarizes the current studies on cardiac repair with VSELs after AMI, and discusses the potential mechanisms and implications of these cells in cardiac repair.