Enhanced external counterpulsation promotes growth cytokines-mediated myocardial angiogenesis in a porcine model of hypercholesterolemia

Background Enhanced external counterpulsation （EECP） improves ischemia in patients with refractory angina pectoris but the mechanism remains unclear. To explore the mechanisms of EECP action, we detected progenitor cells presenting any of the following markers CD34^＋, CD29^＋, and CD106^＋. Methods Growth cytokines-mediated progenitor cell mobilization and associated angiogenesis potential were assessed in a porcine model of hypercholesterolemia. Twenty-four male domestic swines were randomly assigned to 4 groups： normal diet （control, n=6）, hypercholesterolemic diet （CHOL, n=-6）, hypercholesterolemic diet with administration of recombinant human granulocyte colony-stimulating factor （rhG-CSF） （rhG-CSF, n=6）, and hypercholesterolemic diet with EECP treatment （EECP, n=6）. EECP was applied 2 hours every other day for a total of 36 hours. Serum levels of vascular endothelial growth factor （VEGF） and granulocyte colony-stimulating factor （G-CSF）, peripheral blood progenitor cell counts, level of regional angiogenesis, and expression of VEGF and stromal cell derived factor l a （SDF-1α） in porcine myocardium were assessed, respectively. Results A porcine model of hypercholesterolemia-induced arteriosclerosis was successfully established. There was no significant difference in serum levels of VEGF among the four groups. The serum levels of G-CSF in the EECP group increased significantly at week 15 and week 18 （（38.3±5.6） pg/ml at week 15 vs （26.2±3.7） pg/ml at week 12, P 〈0.05, and （46.9±6.1） pg/ml at week 18 vs （26.2±3.7） pg/ml at week 12, P 〈0.01）. The serum levels of G-CSF in group 3 increased also significantly after receiving rhG-CSF injection for five days （（150±13.9） pg/ml at week 18 vs （24.8±5.4） pg/ml at week 12, P 〈0.01）. Compared to other groups and other time points, progenitor celt counts increased significantly after 2-hour EECP treatment （108±13 vs 26±6 per 10^5 leukocytes, P 〈0.01）, but not at week 18. The progenitor cell counts also increased significantly after subcutaneous injection of rhG-CSF for five days compared to the week 12 （baseline） （180±21 vs 25±7 per 10s leukocytes, P 〈0.01）. There was no significant difference among the four groups at other time points. Moreover, the expression of VEGF and SDF-1α and the level of regional angiogenesis in myocardium increased significantly in both EECP and rhG-CSF groups. Conclusions The results demonstrated that EECP could facilitate angiogenesis in the myocardium of atherosclerotic swines by increasing endogenous G-CSF, inducing an enhanced mobilization of progenitor cells and augmenting myocardial expression of VEGF and SDF-1α.

Benidipine has effects similar to losartan on the central blood pressure and arterial stiffness in mild to moderate essential hypertension

Background Central blood pressure （BP） is pathophysiologically more important than peripheral BP for the pathogenesis of cardiovascular disease. Arterial stiffness is also a good predictor of cardiovascular morbidity and mortality. The effects of benidipine, a unique dual L-IT-type calcium channel blocker, on central BP have not been reported. This study aimed to compare the effect of benidipine and Iosartan on the central BP and arterial stiffness in mild to moderate essential hypertensives. Methods This 24 weeks, multi-center, open label, randomized, active drug comparative, parallel group study was designed as a non-inferiority study. The eligible patients （n=200） were randomly assigned to receive benidipine （n=101） or Iosartan （n=99）. Radial artery applanation tonometry and pulse wave analysis were used to measure the central BP, pulse wave velocity （PWV） and augmentation index （AIx）. We also measured the metabolic and inflammatory markers. Results After 24 weeks, the central BP decreased significantly from baseline by （16.8±14.0/10.5±9.2） mmHg （1 mmHg =0.133 kPa） （systolic/diastolic BP; P 〈0.001） in benidipine group and （18.9±14.7/12.1±10.2） mmHg （P 〈0.001） in Iosartan group respectively. Both benidipine and Iosartan groups significantly lowered peripheral BP （P 〈0.001） and AIx （P 〈0.05）, but there were no significant differences between the two groups. The mean aortic, brachial and femoral PWV did not change in both groups after 24-week treatment. There were no significant changes of the blood metabolic and inflammatory biomarkers in each group. Conclusion Benidipine is as effective as Iosartan in lowering the central and peripheral BP, and improving arterial stiffness.