Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004153 (atherosclerosis)
 77,401 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.
 ...
PMID:Androgens and cardiovascular disease. 1278 2

The relationship between erectile dysfunction (ED) and lower urinary tract symptoms (LUTS) caused by benign prostatic obstruction (BPO) has recently gained increasing attention. Both BPO and ED are highly prevalent in older men and both conditions frequently contribute to a reduction in overall quality of life. Current medical treatment of LUTS/BPO consists of monotherapy with alpha(1)-adrenoceptor antagonists or 5alpha-reductase inhibitors, a combination of these two agents or, in some cases, various phytotherapeutic approaches. When choosing a drug therapy, it is important to recognize that while 5alpha-reductase inhibitors increase the risk of ED and ejaculatory disorders, and combined therapy carries the cumulative risk of causing sexual dysfunction, some alpha(1)-adrenergic receptor antagonists have been reported to improve overall sexual function. Therefore, the successful evaluation and management of older men with LUTS associated with BPO should include an assessment of baseline sexual function and subsequent monitoring of medication-induced sexual adverse effects. In this review, we detail the pathophysiological mechanisms involved in LUTS/BPO-associated ED, including reduced nitric oxide/cyclic guanosine monophosphate system activity, enhanced endothelin-1/rhoA/rho kinase pathway activity, sympathetic overactivity, pelvic organ atherosclerosis and potential preventive approaches.
 ...
PMID:Guide to drug therapy for lower urinary tract symptoms in patients with benign prostatic obstruction : implications for sexual dysfunction. 1819 26

Dihydrotestosterone (DHT) originates via irreversible reduction of testosterone by catalytic activity of 5alpha-reductase enzyme and it is demonstratively the most effective androgen. Androgens influence adipose tissue in men either directly by stimulation of the androgen receptor or indirectly, after aromatization, by acting at the estrogen receptor. DHT as a non-aromatizable androgen could be responsible for a male type fat distribution. The theory of non-aromatizable androgens as a potential cause of a male type obesity development has been studied intensively. However, physiological levels of DHT inhibit growth of mature adipocytes. In animal models, substitution of DHT in males after gonadectomy has a positive effect on body composition as a testosterone therapy. Thus, DHT within physiological range positively influences body composition. However, there are pathological conditions with an abundance of DHT, e.g. androgenic alopecia and benign prostatic hyperplasia. These diseases are considered as risk factors for development of metabolic syndrome or atherosclerosis. In obese people, DHT metabolism in adipose tissue is altered. Local abundance of non-aromatizable androgen has a negative effect on adipose tissue and it could be involved in pathogenesis of metabolic and cardiovascular diseases. Increased DHT levels, compared to physiological levels, have negative effect on development of cardiovascular diseases. Difference between the effect of physiological and increased level brings about certain paradox.
 ...
PMID:The role of non-aromatizable testosterone metabolite in metabolic pathways. 2111 70