Prevalence of Myocardial Fibrosis in Intensive Endurance Training Athletes: A Systematic Review and Meta-Analysis.

Objective: To review the published literature reporting on the incidence of myocardial fibrosis (MF) in high-intensity endurance athletes measured by late gadolinium enhancement (LGE) with cardiac magnetic resonance imaging (CMR). Methods: Five databases (PubMed, Cochrane Controlled Trials Register, EMBASE, Web of Science, and SPORTDiscus) were searched to obtain case cohort studies published before November 10, 2019. From 96 abstracts or reports extracted, 18 full-text articles were reviewed. The incidence of LGE was reported as outcome measures. Subgroup analysis was performed by age (under or above 50 years). Pooled estimates were obtained using a fixed-effects model. Results: After a full-text assessment, 12 studies involving 1,359 participants were included for analysis. Among them, 163/772 participants in the endurance athletes group showed LGE positive, compared with 19/587 participants in the comparison group. The results of the meta-analysis suggested that the prevalence of LGE was higher in the athletes group with long-term endurance exercise (OR 7.20;95%CI: 4.51-11.49). In addition, the same conclusion was drawn after the stratification of age. Conclusions: The available evidence demonstrates that high-intensity endurance athletes is associated with an increased incidence of LGE positive.

[Relationship between exercise tolerance and early heart function impairment in patients with acute ST-elevation myocardial infarction and normal left ventricular ejection fraction].

OBJECTIVE: To explore the relationship between early heart function impairment and exercise tolerance in patients with acute ST-elevation myocardial infarction (STEMI) and normal left ventricular ejection fraction (LVEF). METHODS: A total of 229 patients with a LVEF of ≥ 50% were retrospectively reviewed. There were 199 males and 30 females with a mean age of 56.2 ± 11.1 years. They underwent cardiopulmonary exercise testing (CPET) early after STEMI in a single exercise laboratory. Demographic data, presence of concomitant diseases, characteristics of STEMI, echocardiography and CPET findings were evaluated. RESULTS: Their mean LVEF was 60.2% ± 6.9% and the values of Vo(2 peak) and Vo(2AT) were (21.8 ± 5.7) ml×kg(-1)×min(-1) and (19.4 ± 4.8) ml×kg(-1)×min(-1) respectively. Peak oxygen uptake (Vo(2 peak)) showed a positive correlation with LVEF (r = 0.17, P = 0.012), E/A (r = 0.15, P = 0.033) and peak myocardial systolic velocity (Sm) (r = 0.30, P < 0.001). On the contrary, it varied inversely with peak A wave velocity (A) (r = -0.20, P = 0.005), E/Em (r = -0.16, P = 0.022) and left atrial pressure (LAP) (r = -0.16, P = 0.021). And there was a similar correlation between oxygen uptake at anaerobic threshold (Vo(2AT)) and LAP (r = -0.17, P = 0.031). After adjustments of subject demographic features and cardiovascular risk factors, Vo(2 peak) was still associated with LVEF (ß = 0.149, s = 0.051, sß = 0.178, 95%CI 0.048 - 0.250, P = 0.004) and Sm (ß = 0.606, s = 0.167, sß = 0.245, 95%CI 0.277 - 0.936, P < 0.001). So did the relationship between Vo(2AT) and LAP (ß = -0.271, s = 0.117, sß = -0.172, 95%CI -0.501 - -0.040, P = 0.022). CONCLUSION: The exercise tolerance may be affected by early heart function impairment in STEMI patients. CPET is a sensitive detection tool of decreased heart function.

Hepatocyte growth factor plays a critical role in the regulation of cytokine production and induction of endothelial progenitor cell mobilization: a pilot gene therapy study in patients with coronary heart disease.

1. There is growing evidence of the beneficial effects of hepatocyte growth factor (HGF) in myocardial infarction, heart failure and occlusive peripheral arterial disease. The aim of the present study was to evaluate the effects of intracoronary administration of an adenovirus vector encoding the human HGF gene (Ad-HGF) on serum levels of cytokines and mobilization of CD34(+) and CD117(+) cells in patients with coronary heart disease. 2. Twenty-one patients with severe coronary artery disease were recruited to the study: 11 patients received both a stent and administration of Ad-HGF; the remaining 10 patients received a stent alone and served as the control group. Blood samples were obtained from the femoral vein before and then 6 and 24 h, 3 and 6 days and 2 weeks after treatment for the isolation of serum and peripheral blood mononuclear cells. Intracoronary administration of Ad-HGF in patients with coronary heart disease resulted in high levels of HGF gene expression, as well as its receptor c-met, compared with the control group, as demonstrated by real-time reverse transcription-polymerase chain reaction. In addition, serum levels of HGF, vascular endothelial growth factor, monocyte chemoattractant protein-1 and interleukin (IL)-10 were increased and serum levels of IL-8 were decreased in patients administered Ad-HGF compared with the control group. The percentage of CD34(+) and CD117(+) cells in the peripheral blood increased in patients administered Ad-HGF. 3. In conclusion, HGF gene therapy may play an important role in the regulation of cytokines and the induction of endothelial progenitor cell mobilization in patients with coronary heart disease.

Neovascularization and cardiomyocytes regeneration in acute myocardial infarction after bone marrow stromal cell transplantation: comparison of infarct-relative and noninfarct-relative arterial approaches in swine.

BACKGROUND: Adult bone marrow stromal cells could differentiate into myogenic endothelial progenitor cells and has been investigated for the potential value in regeneration. Recently, it has been reported that bone marrow cells (BMCs) are able to repair the infracted myocardium by intracoronary transplantation via infarct-related artery in humans. Unfortunately, we cannot open the infarcted artery by traditional reperfusion therapies in some patients. We investigate the hypothesis that BMCs transplantation might get the same effect via noninfarct-relative artery. This alternative approach may have potential application in clinical practice. METHODS: A swine myocardial infarction model was established by distal left anterior descending artery ligation. Bone marrow stromal cells isolated, culture-expanded and labeled with bromodeoxyuridine (BrdU) were used as donor cells. Four weeks after coronary artery ligation, either a graft of 5x10(6) donor cells (n=12) or culture medium (n=6) was infused into infarcted area via infarct-relative artery (left coronary artery, n=6) and noninfarct-relative artery (right coronary artery, n=6). Heart function was evaluated by gate cardiac perfusion imaging before the transplantation and 4 weeks after transplantation. The donor cell localization and differentiation were identified by immunohistochemical staining for BrdU and beta-myosin heavy chain (beta-MHC) and angiogenesis was assessed by immunohistochemical staining for alpha-smooth muscle actin (alpha-SMA) and Factor VIII. RESULTS: Gate cardiac perfusion imaging demonstrated that the cardiac function was significantly improved after the stromal cell transplantation via both infarct-relative and noninfarct-relative coronary arteries compared with control group (45.03+/-2.71 and 47.78+/-2.64 vs 30.36+/-2.76, P<0.05). Four weeks after transplantation, BrdU and beta-MHC positive cells were detected within the infarct area. Vessel densities in infarct area and infarct border area were increased significantly in both transplantation groups compared to the control group (98.68+/-5.32 and 87.49+/-6.04 vs 48.46+/-4.88, P<0.05). CONCLUSIONS: Transplantation of bone marrow stromal cell via both infarct-relative and noninfarct-relative coronary arteries improved heart function in the myocardial infarction animals by stimulating cardiomyocyte regeneration and angiogenesis.

Induction of collateral artery growth and improvement of post-infarct heart function by hepatocyte growth factor gene transfer.

AIM: To study the effect of adenovirus5-mediated human hepatocyte growth factor (Ad(5)-HGF) transfer on post-infarct heart failure in a swine model. METHODS: Twelve young Suzhong swine were randomly divided into 2 groups: the Ad(5)-HGF group (n=6) and the null-Ad(5) group (n=6). Four weeks after left anterior descending coronary artery (LAD) ligation, Ad5-HGF was transferred into the myocardium via the right coronary artery. Coronary angiography and gated cardiac perfusion imaging were performed at the end of 4 and 7 weeks after LAD ligation, respectively, to evaluate collateral artery growth and cardiac perfusion. Then all animals were killed, the expression of HGF and alpha-smooth muscle actin (alpha-SMA) were evaluated by enzyme-linked immunosorbent assay and immunohistochemistry. RESULTS: Compared with the null-Ad(5) group, higher expression of human HGF was observed in the myocardium in the Ad(5)-HGF group (109.3+/-7.8 vs 6.2+/-2.6, t=30.685, P<0.01). The left ventricular ejection fraction was higher in the Ad(5)-HGF group than in the null-Ad(5) group (43.9+/-4.3 vs 30.4+/-2.8, t=6.514, P<0.01). From the 4th week to the 7th week after operation, left ventricular end systolic volume (42.1+/-3.0 vs 31.0+/-4.9, t=12.800, P<0.01) and left ventricular end diastolic volume (62.2+/-4.2 vs 55.0+/-4.8 t=13.207, P<0.01) were improved in the Ad(5)-HGF group. Cardiac perfusion was significantly improved in the Ad(5)-HGF group. In the Ad(5)-HGF group, growth of collateral arteries was obviously greater (average rank sum 9.17 vs 3.83, n=6, u=-2.687, P<0.01), and the number of alpha-SMA(+) vessels/mm(2) was significantly greater (56.1+/-4.2 vs 16.4+/-3.5, t=17.731, P<0.01) than in the null-Ad(5) group. CONCLUSION: High expression levels of human HGF were observed in the myocardium because of non-infarct-related vessel transfer. HGF can increase the number of functional arterioles and improve collateral artery growth. HGF can improve cardiac perfusion and heart function.

[Hepatocyte growth factor did not enhance the effects of bone marrow-derived mesenchymal stem cells transplantation on cardiac repair in a porcine acute myocardial infarction model].

OBJECTIVE: To evaluate the impact of combined therapy with transplanting bone marrow-derived mesenchymal stem cells (BM-MSCs) via noninfarct-relative artery and hepatocyte growth factor (HGF) in a porcine myocardial infarction (MI) model. METHODS: BM-MSCs were obtained from pig bone marrow, expanded in vitro with a purity of > 50%. MI was induced by ligating the distal left anterior descending artery in pigs. Eighteen animals received BM-MSCs cells (5 x 10(6)/ml, n = 6), BM-MSCs cells (5 x 10(6)/ml) plus HGF (4 x 10(9) pfu, n = 6) or equal volume culture medium (IMDM) via non-infarct-related artery at four weeks after MI. Gated myocardial perfusion imaging and coronary angiography were performed before and four weeks after transplantations. Histological examination was also performed 4 weeks after transplantation. RESULTS: LVEF measured by gated myocardial perfusion imaging was similar among groups before transplantation and significantly increased in BM-MSCs (45 +/- 3 vs. 34 +/- 2%, P < 0.05) or BM-MSCs + HGF (46 +/- 6 vs. 34 +/- 3%, P < 0.05) treated animals while remained unchanged in IMDM (30 +/- 3 vs. 32 +/- 2%) treated animals 4 weeks post transplantation. Similarly, capillary density was also significantly higher and myocardial perfusion defect scores significantly decreased in BM-MSCs or BM-MSCs + HGF treated hearts than that in IMDM treated hearts. However, all these changes were similar between BM-MSCs and BM-MSCs + HGF groups. Rentrop score was similar before and 4 weeks after transplantation among various groups. CONCLUSION: HGF in combination with BM-MSCs transplantation did not enhance the cardiac repair effects of BM-MSCs transplantation alone and BM-MSCs transplantation did not improve collateral circulation in this model.

[Effects of LbGp on the intracellular free calcium concentration of cardiomyocytes induced by hypoxia and KCl].

OBJECTIVE: Hypoxia/KCl injury model in the cultured neonatal rat cardiomyocytes (CMs) was established to investigate the protective effect of Lycium barbanun Glycopeptide (LbGp) on calcium overload. METHOD: Cultured neonatal rat CMs were divided into three groups, namely normal control, hypoxia groups and LbGp-treated group. CMs in LbGp-treated group and hypxia group were cultured in an incubator ventilated with 95% N2 and 5% CO2 with or without LbGP. CMs viability under hypoxia was measured by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide colorimetry (MTT). The intracellular free calcium concentration in cardiomyocytes was measured by laser confocal microscope with Fura-3/AM as a calcium indicator. The protective effects of LbGp on the CMs treated by KCl (60 mmol x L(-1)) was observed. RESULT: As compared with normal controls, the degree of MTT metabolism was significantly reduced (P < 0.01) in hypoxic group and slightly reduced in LbGp (P < 0.05). Hypoxia-induced enhancement of intracellular calcium ([Ca2+]i) was attenuated by LbGp significantly (P < 0.01). Moreover, KCl-induced enhancement of [Ca2+]i was also reduced by LbGp at the doses of 25, 50, 100 microg x mL(-1) in a concentration-dependent manner. CONCLUSION: The result suggested that LbGp is able to increase the survival ratio and inhibit the enhancement of the intracellular free calcium concentration in cardiomyocytes induced by hypoxia and high potassium. One of the mechanisms is that LbGp acts on L-type calcium channels.