P Collins's research while affiliated with Imperial College London and other places

... and the ACE gene I/D polymorphism (31,32). Moreover, cigarette smoking is another environmental and important risk factor for CAD in Turkish population (25). ...

... Recently, three placebo-controlled studies carried out during cardiac catheterization in postmenopausal women with coronary atherosclerosis confirmed the previous observations in monkeys, showing reversion of the paradoxical vasoconstriction induced by acetylcholine with acute estrogen use [74][75][76] . In one of these studies 75 , estrogen administration also resulted in coronary vasodilatation and in flow increase at the basal state (preacetylcholine). ...

... 66 Mixed results have been shown in the treatment of CSX patients. While several small controlled prospective studies of transdermal estrogen therapies demonstrate a reduction of chest pain episodes 107 and time to ischemia on stress testing, 108 there is also evidence that symptomatic benefits are attenuated in longer duration treatments. 109 Given the current controversy over HRT in cardiovascular disease disease prevention, this therapy is not currently recommended. ...

... 14 15 The net result of oestrogen action is to cause vasodilatation, although this is antagonised to some extent by the progestin or progesterone. 16 The mechanisms of this vasodilator eVect have been examined in both ex vivo and in vivo models. Collins and colleagues showed that when oestradiol is injected into atheromatous human female coronary arteries, the atheromatous paradoxical constrictor eVect in response to acetylcholine is reversed and the arteries dilate normally. ...

... Estrogens are known to modify the levels of lipid fractions , retarding the development of atherosclerotic plaques, ameliorating endothelial function and stimulating the synthesis of nitric oxide. In experimental models estrogen relaxes the endothelin-induced vessel contraction, augments the synthesis of prostacyclin in smooth muscle cell cultures and possibly directly inhibits calcium channels causing vessel relaxation (Rosano et al., 1993; Mendelsohn & Karas, 1999; Binko & Majewski, 1998 ). The estrogens reduce inflammatory state via modulation of expression of adhesion molecules, they also participate in myocardial protection (ischemic preconditioning). ...

... This latter observation shed doubts on the safety of MPA-oestrogen preparations in cardiovascular sensitive individuals. Contrasting with these findings, the vaginal progesterone gel does not alter the beneficial effects of oestrogens on CHD (Rosano et al., 1996). On the contrary, vaginal progesterone in coronary symptomatic women appears to exert beneficial effects of its own (Rosano et al., 1996), beyond those mediated by oestrogen treatment. ...

... Indeed, gender differences in smooth muscle reactivity may be related to differential expression and/or activity of sex hormone receptors (25), effects of sex hormones on the gene expression of the specific receptors of contractile agonists (26), or sex-related differences in the signaling mechanisms of smooth muscle contraction downstream from receptor activation (1). It is established that phosphorylation of Ser19 on the regulatory light chain of myosin II by Ca 2+ /calmodulin-dependent MLCK is essential for the initiation of smooth muscle contraction (27). ...

... uggested that the VSMC-derived nNOS has a role in the relaxation of isolated porcine coronary arteries (Han et al., 2009). The identified mechanism for relaxation is via E2-initiated phosphatidylinositol 3-kinase- Akt signaling, leading to rapid nNOS activation and NO/ cGMP-mediated opening of calcium-activated potassium channels (BK Ca ) on VSMCs. Rosano et al. (1993) propose this endothelium-independent mechanism to explain the clinical observation that E2 is able to enhance coronary blood flow in diseased coronary arteries with dysfunctional endothelium. Differences between sexes in vascular function are now well recognized at various levels: from populations and subjects , extending into fundament ...

... Inhibition of voltage-gated calcium influx by acute application of estrogen was shown very early in a variety of cardiac cells and tissues such as isolated adult ventricular myocytes of guinea pigs [107][108][109], isolated adult ventricular myocytes of rats [109,110], rat aorta [111], rabbit coronary arteries [112], rabbit arterial tissue [113], isolated atrial myocytes from human hearts [109] and vascular smooth muscles of rats and rabbits [114]. In most of these studies, inhibition of inward voltage-gated calcium current by estrogen was achieved within minutes (with a time constant of 3-4 s) and IC 50 values obtained in the presence and absence of ER antagonist ICI 182780 were similar, indicating that antagonizing ERs did not alter estrogen effect; therefore, perhaps the mechanism of action of estrogen did not involve classical hormonal receptor activation [111]. ...

... Although endurance exercise training improves muscle PO 2 mv kinetics (potentially via a speeding of the f RBC response as discussed above) following the onset of contractions in both healthy (26) and CHF (present investigation) rats, enhanced NO signaling does not appear to be intrinsic to training-induced adaptations in muscle microvascular O 2 exchange in CHF ϩ EXT (Figs. 1-4 and Table 3). Despite evidence supporting an improvement in NO-induced vasodilation in CHF after exercise training (24,40,66), it is interesting to note that Lindsay et al. (39) reported no effects of training on acetylcholine-induced relaxation of aortic rings in CHF rats and Yi et al. (68) found preserved prostaglandininduced relaxation of coronary arteries from trained CHF dogs. Together with the fact that impairments in NO-mediated function with CHF might be compensated by increased contribution of other vasodilators such as endothelium-derived hyperpolarizing factors (EDHF) (33,42), these data highlight the redundancy and synergism of mechanisms regulating muscle O 2 delivery (25) and suggest that exercise training may alter the relative contribution of distinct mechanisms governing microvascular oxygenation in CHF. ...