Aims Heart failure (HF) is associated with increased large conduit artery stiffness and afterload resulting in stiffening of the coronary arteries. Perivascular adipose tissue (PVAT) and advanced glycation end products (AGE) both promote arterial stiffness, yet the mechanisms by which coronary PVAT promotes arterial stiffness and the efficacy of exercise to prevent coronary stiffness are unknown. We hypothesized both chronic continuous and interval exercise training would prevent coronary PVAT-mediated AGE secretion and arterial stiffness. Methods and Results Yucatan mininature swine were divided into four groups: control-sedentary (CON), aortic-banded sedentary heart failure (HF), aortic-banded HF continuous exercise trained (HF+CONT), and aortic-banded HF interval exercise trained (HF+IT). The left circumflex (LCX) and right coronary artery (RCA) underwent ex vivo mechanical testing, and arterial AGE, elastin and collagen were assessed. Coronary elastin elastic modulus (EEM) and elastin protein were lower, and AGE was increased with HF compared to CON that was prevented by both HF+CONT and HF+IT. Mouse aortic segments treated with swine coronary PVAT-conditioned media had lower EEM, elastin content, greater AGE secretion and arterial AGE accumulation in HF compared with CON, which was prevented by both HF+CONT and HF+IT. Aminoguanidine (AMG), an AGE inhibitor, prevented the reduction in the EEM, arterial elastin content and AGE accumulation in mouse aortic segments treated with PVAT conditioned media in the HF group. Conclusions Our data demonstrate efficacy for chronic continuous and interval exercise to prevent coronary artery stiffness via inhibition of PVAT-derived AGE secretion in a pre-clinical mini-swine model of pressure overload-induced HF.

Consumption of a high-fat, high-sugar diet and sedentary lifestyle are correlated with bulk arterial stiffening. While measurements of bulk arterial stiffening are used to assess cardiovascular health clinically, they cannot account for changes to the tissue occurring on the cellular scale. The compliance of the subendothelial matrix in the intima mediates vascular permeability, an initiating step in atherosclerosis. High-fat, high-sugar diet consumption and a sedentary lifestyle both cause micro-scale subendothelial matrix stiffening, but the impact of these factors in concert remains unknown. In this study, mice on a high-fat, high-sugar diet were treated with aerobic exercise or returned to a normal diet. We measured bulk arterial stiffness through pulse wave velocity and subendothelial matrix stiffness ex vivo through atomic force microscopy. Our data indicate that while diet reversal mitigates high-fat, high-sugar diet-induced macro- and micro-scale stiffening, exercise only significantly decreases micro-scale stiffness and not macro-scale stiffness, during the time-scale studied. These data underscore the need for both healthy diet and exercise to maintain vascular health. These data also indicate that exercise may serve as a key lifestyle modification to partially reverse the deleterious impacts of high-fat, high-sugar diet consumption, even while macro-scale stiffness indicators do not change.

Introduction:The increasing blood glucose level due to insulin resistance which occurs in diabetes mellitus (DM) may cause vascular damage. This study aims to prove the effect of the polysaccharide peptide (PsP)on improving vascular damage through an increase of circulating endothelial cells and circulating endothelial cells (CEC) ratio, decreased H2O2, triglyceride (TG), total cholesterol (TC) and insulin resistance in type 2 DM.

Methods:Our study is a true experimental study with randomized posttest control group design that used 35 Wistar rats divided into five groups: normal, control (+) and three groups of different variant PsP doses 50, 150 and 300 mg/kg BW (n=7).

Results:By using one-way ANOVA and post-hoc Duncan test, the results show a significant increase of endothelial progenitor cell (EPC) concentration (=0.000) and ratio EPC:CEC (0.000) by dose-dependent fashion and also reduced CEC concentration (=0.001), H2O2 (=0.03), TG (=0.001), TC (=0.01) and insulin resistance (=0.003).

Conclusion:In this study, PsP induced endothelial repairing process and reduced the risk factor with 300 mg/kg BW as optimum dose. However, further research on EPC and CEC detection markers is important. Further research on PsP and clinical trial for commercial uses is also needed.