Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Globally, cardiovascular disease will continue causing most human deaths for the foreseeable future. The consistent gender gap in life span of approximately 5.6 yr in all advanced economies must derive from gender differences in age-specific cardiovascular death rates, which rise steeply in parallel for both genders but 5-10 yr earlier in men. The lack of inflection point at modal age of menopause, contrasting with unequivocally estrogen-dependent biological markers like breast cancer or bone density, makes estrogen protection of premenopausal women an unlikely explanation. Limited human data suggest that testosterone exposure does not shorten life span in either gender, and oral estrogen treatment increases risk of cardiovascular death in men as it does in women. Alternatively, androgen exposure in early life (perinatal androgen imprinting) may predispose males to earlier onset of atherosclerosis. Following the recent reevaluation of the estrogen-protection orthodoxy, empirical research has flourished into the role of androgens in the progression of cardiovascular disease, highlighting the need to better understand androgen receptor (AR) coregulators, nongenomic androgen effects, tissue-specific metabolic activation of androgens, and androgen sensitivity. Novel therapeutic targets may arise from understanding how androgens enhance early plaque formation and cause vasodilatation via nongenomic androgen effects on vascular smooth muscle, and how tissue-specific variations in androgen effects are modulated by AR coregulators as well as metabolic activation of testosterone to amplify (via 5alpha-reductase to form dihydrotestosterone acting on AR) or diversify (via aromatization to estradiol acting upon estrogen receptor alpha/beta) the biological effects of testosterone on the vasculature. Observational studies show that blood testosterone concentrations are consistently lower among men with cardiovascular disease, suggesting a possible preventive role for testosterone therapy, which requires critical evaluation by further prospective studies. Short-term interventional studies show that testosterone produces a modest but consistent improvement in cardiac ischemia over placebo, comparable to the effects of existing antianginal drugs. By contrast, testosterone therapy has no beneficial effects in peripheral arterial disease but has not been evaluated in cerebrovascular disease. Erectile dysfunction is most frequently caused by pelvic arterial insufficiency due to atherosclerosis, and its sentinel relationship to generalized atherosclerosis is insufficiently appreciated. The commonality of risk factor patterns and mechanisms (including endothelial dysfunction) suggests that the efficacy of antiatherogenic therapy is an important challenge with the potential to enhance men's motivation for prevention and treatment of cardiovascular diseases.
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PMID:Androgens and cardiovascular disease. 1278 2

Stroke stimulates cell proliferation in the subventricular zone (SVZ) and hippocampal dentate gyrus (DG) in adult rodents and humans. However, most newborn cells will die within 1-2 weeks. We recently have revealed that progesterone (P4) promotes the survival of newborn neurons in the DG and improves the neurological dysfunction after cerebral ischemia. The aim of this study was to further explore the effects of P4 on the ischemia-induced neurogenesis in the DG, SVZ and striatum. Bromodeoxyuridine (BrdU) was used to label proliferating cells on day 3 after middle cerebral artery occlusion (MCAO). P4 (4 mg/kg) was injected for 3 consecutive days at BrdU-D(-1 to 1) (from one day before to one day after BrdU-injection) or BrdU-D(4-6) (4-6 days after BrdU-injection). The P4-treatment at BrdU-D(-1 to 1) attenuated the increase in the density of 24-h-old BrdU(+) cells in MCAO-DG and -SVZ, which was blocked by the 5alpha-reductase inhibitor finasteride. The P4-treatment at BrdU-D(4-6) significantly increased the density of 28-day-old BrdU(+) cells in MCAO-DG without changing the population ratios of BrdU(+)/NeuN(+) and BrdU(+)/GFAP(+) cells, which was sensitive to the blockade of P4 receptor and extracellular signal-regulated kinase (ERK). In addition, the P4-treatment at BrdU-D(4-6) produced approximately 2-fold increase in the density of 28-day-old BrdU(+) cells in MCAO-striatum. This study provides evidence that the P4-treatment after stroke suppresses ischemia-stimulated proliferation of progenitor cells but improves the poor survival of ischemia-induced newborn cells.
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PMID:Treatment with progesterone after focal cerebral ischemia suppresses proliferation of progenitor cells but enhances survival of newborn neurons in adult male mice. 2007 61