Background-Enhanced external counterpulsation (EECP) is a circulation assist device that may improve endothelial dysfunction by increasing shear stress. Chronic exposure of vascular endothelial cells and vascular smooth muscle cells to relatively high physiological shear stress has antiproliferative and vasoprotective effects. The present study hypothesizes that EECP inhibits intimal hyperplasia and atherogenesis by modifying shear stress-responsive gene expression. Methods and Results-Thirty-five male pigs were randomly assigned to 3 groups: high-cholesterol diet (nϭ11), high-cholesterol diet plus EECP (nϭ17), and usual diet (control; nϭ7). The coronary arteries and aortas were collected for histopathological study and immunohistochemical and Western blot analysis. The peak diastolic arterial wall shear stress during EECP increased significantly compared with before EECP (49.62Ϯ10.71 versus 23.92Ϯ7.28 dyne/cm 2 ; PϽ0.001). Intimal hyperplasia was observed in the coronary arteries of the high-cholesterol diet group, whereas in animals receiving EECP, the intima-to-media area ratio was significantly decreased by 41.59% (21.27Ϯ10.00% versus 36.41Ϯ16.69%; Pϭ0.008). Hypercholesterolemia attenuated the protein expression of endothelial NO synthase and enhanced the phosphorylation of extracellular signal-regulated kinases 1/2. EECP treatment alleviated these adverse changes. Conclusions-EECP reduces hypercholesterolemia-induced endothelial damage, arrests vascular smooth muscle cell proliferation and migration, decreases proliferating cell nuclear antigen proliferative index, suppresses extracellular matrix formation, and eventually inhibits intimal hyperplasia and the development of atherosclerosis by increasing the arterial wall shear stress, which in turn activates the endothelial NO synthase/NO pathway and probably suppresses extracellular signal-regulated kinases 1/2 overactivation. (Circulation. 2007;116:526-534.)

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Heart failure is the terminal outcome of the majority of cardiovascular diseases, which lacks specific diagnostic biomarkers and therapeutic targets. It contributes to most of cardiovascular hospitalizations and death despite of the current therapy. Therefore, it is important to explore potential molecules improving the diagnosis and treatment of heart failure. MicroRNAs (miRNAs) are small non-coding RNAs that have been reported to be involved in regulating processes of heart failure. After the discovery of miRNAs in exosomes, the subcellular distribution analysis of miRNAs is raising researchers' attention. Growing evidence demonstrates that exosomal miRNAs may be promising diagnostic and therapeutic molecules for heart failure. This review summarizes the role of exosomal miRNAs in heart failure in the prospect of molecular and clinical researches.

Accumulating evidence indicates that angiotensin-(1-7) [Ang-(1-7)] offers protective effects against ischemia-reperfusion (I/R) induced arrhythmias and contractile dysfunction, which are related to disturbances of intracellular calcium homeostasis. However, whether or not Ang-(1-7) regulates intracellular calcium in I/R is not clear. To shed light on this issue, we carried out studies with a cellular model of simulated I/R in isolated rat ventricular myocytes and measured calcium transients using laser scanning confocal microscopy. Our results showed that Ang-(1-7) had no effects on the calcium transient in myocytes superfused with normal solution; however, in myocytes of simulated I/R, Ang-(1-7) significantly attenuated the increased diastolic intracellular Ca during reperfusion, restored the decreased peak Ca of calcium transient during ischemia, and reversed the decreased amplitude of calcium transient throughout the I/R periods. Additionally, Ang-(1-7) significantly suppressed the reactive oxygen species production in I/R, especially during the ischemic phase. These data indicated that Ang-(1-7) affords significant cytoprotective effects through directly improving calcium homeostasis independent of its anti-oxidative action. Most notably, the effects of Ang-(1-7) on intracellular Ca dynamics manifests only in the diseased states, that is, I/R. This unique property suggests that upregulation of Ang-(1-7) expression and/or activation of the Ang-(1-7)/Mas signaling cascade is a highly desirable strategy for the treatment of myocardial impairment induced by I/R.

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Background It remains unknown whether admission mean (MAP) and pulse (PP) pressure are associated with short and longterm mortality in Chinese patients with heart failure with preserved (HFpEF), midrange (HFmrEF), and reduced (HFrEF) ejection fraction. Methods In 2706 acute decompensated HF patients, we assessed the risk of 30day, 1 year, and longterm (>1 year) mortality with 1SD increment in MAP and PP, using multivariable logistic and Cox regression, respectively. Results During a median follow up of 4.1 years, 1341 patients died. The 30day, 1year, and longterm mortality were 3.5%, 16.7%, and 39.4%, respectively. A lower MAP was associated with higher risk of 30day mortality in women (P=0.023) and higher risk of 30day and 1year mortality in men (P≤0.006), while higher PP predicted longterm mortality in men (P≤0.014) with no relationship observed in women. In adjusted analyses additionally accounted for PP, 1SD increment in MAP was associated with 30day mortality in HFpEF (Odds ratio [OR], 0.63; 95% CI, 0.43-0.92; P=0.018), with 1year mortality in HFmrEF (OR, 0.46; 95% CI, 0.32-0.66; P<0.001) and HFrEF (OR, 0.54; 95% CI, 0.40-0.72; P<0.001). In adjusted model additionally accounted for MAP, 1-SD increment in PP was associated with longterm mortality in HFpEF (hazard ratio, 1.16; 95% CI, 1.05-1.28; P=0.003). Conclusions A lower MAP was associated with higher risk of shortterm mortality in all HF subtypes, while a higher PP predicted higher risk of longterm mortality in men and in HFpEF. Our observations highlight the clinical importance of admission blood pressure for risk stratification in HF subtypes.