Everolimus-eluting stents, as compared with paclitaxel-eluting stents, resulted in reduced rates of target-lesion failure at 1 year, results that were consistent in all patients except those with diabetes, in whom the results were nonsignificantly different. (ClinicalTrials.gov number, NCT00307047.)

Short-term administration of testosterone induces a sex-independent vasodilation in coronary conductance and resistance arteries in vivo. Acute testosterone-induced coronary vasodilation of epicardial and resistance vessels is mediated in part by endothelium-derived NO. ATP-sensitive K+ channels appear to play a role in the vasodilatory effect of testosterone in resistance arteries.

Abstract. The effect of cyclic mechanical strain on growth of neonatal rat vascular smooth muscle (VSM) cells were examined. Cells were grown on silicone elastomer plates subjected to cyclic strain (60 cycle/ min) by application of a vacuum under the plates. A 48 h exposure to mechanical strain increased the basal rate of thymidine incorporation by threefold and increased cell number by 40% compared with cells grown on stationary rubber plates. Strain also increased the rate of thymidine incorporation in response to ot-thrombin (from 15-to 33-fold), but not to PDGE As determined by thymidine autoradiography, strain alone induced a fourfold increase in labeled nuclei at the periphery of dishes, where strain is maximal, and a 2-3-fold increase at the center of dishes. Strain appeared to induce the production of an autocrine growth factor(s), since conditioned medium from cells subjected to strain induced a fourfold increase in DNA synthesis in control cells. Western blots of medium conditioned on the cells subjected to strain indicate that the cells secrete both AA and BB forms of PDGF in response to strain. Northern blots of total cell RNA from cells exposed to strain for 24 h show increased steady-state level of mRNA for PDGF-A. Lastly, polyclonal antibodies to the AA form of PDGF reduced by 75 % the mitogenic effect of strain and polyclonal antibodies to AB-PDGF reduced mitogenicity by 50%. Antibodies to bFGF did not significantly reduce the strain-induced thymidine incorporation.

Cyclic mechanical strain (1 Hz) causes a mitogenic response in neonatal rat vascular smooth muscle cells due to production and secretion of PDGF. In this study, the mechanism for sensing mechanical strain was investigated. Silicone elastomer strain plates were coated at varying densities with elastin, laminin, type I collagen, fibronectin, or vitronectin. Strain was applied by cyclic application of a vacuum under the dishes. Cells adhered, spread, and proliferated on each matrix protein, but the mitogenic response to strain was matrix dependent. Strain increased DNA synthesis in cells on collagen, fibronectin, or vitronectin, but not in cells on elastin or laminin. When strain was applied on matrices containing both laminin and vitronectin, the mitogenic response to strain depended upon the vitronectin content of the matrix. Fibronectin, in soluble form (0-50 jg/ml), and the integrin binding peptide GRGDTP (100 ,ug/ml) both blocked the mitogenic response to mechanical strain in cells grown on immobilized collagen. Neither soluble laminin nor the inactive peptide GRGESP blocked the response to strain. GRGDTP did not alter the mitogenic response to exogenous PDGF or a-thrombin but did prevent the secretion of PDGF in response to strain. Furthermore, GRGDTP, but not GRGESP, prevented strain-induced expression of a PDGF-A chain promoter 890 bp-chloramphenicol acetyltransferase construct that was transiently transfected into vascular smooth muscle cells. Finally, the response to strain was abrogated by antibodies to both 83 and avJ5 integrins but not by an antibody to PBu integrins. Thus interaction between integrins and specific matrix proteins is responsible for sensing mechanical strain in vascular smooth muscle cells. (J. Clin. Invest. 1995. 96:2364-2372

Female sex hormones have been implicated in the cardioprotection of premenopausal women. However, the cardiovascular actions of these hormones and the effects of their natural fluctuations during the menstrual cycle are not fully understood. We studied changes in vascular function during the menstrual cycle in 15 healthy premenopausal women. Four noninvasive procedures were performed during the early follicular (EF), late follicular (LF), early luteal (EL), and late luteal (LL) phases: flow-mediated dilatation (FMD) of the brachial artery during reactive hyperemia, laser Doppler velocimetry (LDV) with direct current iontophoresis of acetylcholine (ACh) and nitroprusside, whole body arterial compliance (WBAC), and pulse wave velocity. Hormone levels were consistent with predicted cycle phase and showed that all subjects ovulated during the cycle studied. FMD, LDV with ACh, and WBAC varied cyclically, with significant increases from the F to LF phase, sharp falls in the EL phase, and significant recoveries in the LL phase. These changes were most marked IT IS WELL established that the incidence of coronary heart disease (CHD) in women at all ages is lower than that in men and increases after menopause, when ovarian secretion of sex hormones is low (1, 2). There is evidence that postmenopausal E-containing hormonal therapy reduces CHD risk (3), suggesting that ovarian hormones may provide protection against CHD in premenopausal women. This is supported by the known actions of female sex hormones on the cardiovascular system, which include effects on plasma lipid levels (4) and direct (5, 6) and indirect (7, 8) actions on vessel wall physiology. In addition, the natural hormonal fluctuations during the menstrual cycle are reflected in cardiovascular changes. For example, total plasma cholesterol, low density lipoprotein cholesterol, and apolipoprotein A1 concentrations decrease and high density lipoprotein cholesterol and apolipoprotein (a) increase during the luteal phase compared with the follicular phase (9 -11), and many circulating factors, such as nitric oxide synthase (12), vascular endothelial growth factor (13), and P-selectin (14), demonstrate cyclical variation. It has also been shown that decreases occur in large vessel endothelial function (15) and radial arterial distensibility (16) in the late luteal phase and in cutaneous vasodilatation in the menstrual compared with the follicular phase (17). However, there have been no studies that have documented in detail the changes occurring simultaneously in large and small vessel endothelial function, nonendothelial smooth muscle function, and arterial elasticity or compliance both within and between follicular and luteal phases of the normal menstrual cycle.A detailed understanding of variations in cardiovascular function during the menstrual cycle is of importance for three reasons: it may assist with the interpretation of vascular parameters in premenopausal women; it may provide insights into the mechanisms underlying sex differences in cardiovascular ri...