Impact of inactivity and exercise on the vasculature in humans

The effects of inactivity and exercise training on established and novel cardiovascular risk factors are relatively modest and do not account for the impact of inactivity and exercise on vascular risk. We examine evidence that inactivity and exercise have direct effects on both vasculature function and structure in humans. Physical deconditioning is associated with enhanced vasoconstrictor tone and has profound and rapid effects on arterial remodelling in both large and smaller arteries. Evidence for an effect of deconditioning on vasodilator function is less consistent. Studies of the impact of exercise training suggest that both functional and structural remodelling adaptations occur and that the magnitude and time-course of these changes depends upon training duration and intensity and the vessel beds involved. Inactivity and exercise have direct “vascular deconditioning and conditioning” effects which likely modify cardiovascular risk

Exercise and Peripheral Arteriosclerosis

Adaptation of a healthy lifestyle including adequate daily physical activity is shown to reduce 80% of cardiovascular mortality and 40% of cancer-related deaths. A large body of evidence exists proving that this relationship is dose dependent, and even half of the recommended normal physical activity yields significant risk reduction. There has been no medical therapy that would provide such high percentages of reduction in mortality to date. The World Health Organization, therefore, has started an initiative to implement exercise into daily life as a primary prevention measure. Herein, we will focus on the effects of exercise on the vasculature, mainly the peripheral vasculature, in the context of atherosclerotic disease. Exercise has a fundamental role in the pathogenesis, diagnosis, and treatment of atherosclerotic vascular disease. It exerts a protective effect against the development of atherosclerosis irrespective of other cardiovascular risk factors. Additionally, exercise induces changes in vascular hemodynamics helping us to elucidate the presence of obscure vascular involvement. Once again, exercise is the main treatment modality in peripheral arterial disease with accumulating evidence to reduce symptoms and improve both exercise capacity and cardiovascular symptoms

Association of germline microRNA SNPs in pre-miRNA flanking region and breast cancer risk and survival: the Carolina Breast Cancer Study

PURPOSE: Common germline variation in the 5′ region proximal to precursor (pre-) miRNA gene sequences is evaluated for association with breast cancer risk and survival among African Americans and Caucasians. METHODS: We genotyped 9 single nucleotide polymorphisms (SNPs) within 6 miRNA gene regions previously associated with breast cancer, in 1972 cases and 1776 controls. In a race-stratified analysis using unconditional logistic regression, odds ratios (OR) and 95% confidence intervals (CI) were calculated to evaluate SNP association with breast cancer risk. Additionally, hazard ratios (HR) for breast cancer-specific mortality were estimated. RESULTS: 2 miR-185 SNPs provided suggestive evidence of an inverse association with breast cancer risk (rs2008591, OR = 0.72 (95% CI = 0.53 – 0.98, p-value = 0.04) and rs887205, OR = 0.71 (95% CI = 0.52 – 0.96, p-value = 0.03), respectively) among African Americans. Two SNPs, miR-34b/34c (rs4938723, HR = 0.57 (95% CI = 0.37 – 0.89, p-value = 0.01)) and miR-206 (rs6920648, HR = 0.77 (95% CI = 0.61 – 0.97, p-value = 0.02)), provided evidence of association with breast cancer survival. Further adjustment for stage resulted in more modest associations with survival (HR = 0.65 (95% CI = 0.42 – 1.02, p-value = 0.06 and HR = 0.79 (95% CI = 0.62 – 1.00, p-value = 0.05, respectively). CONCLUSIONS: Our results suggest that germline variation in the 5' region proximal to pre-miRNA gene sequences may be associated with breast cancer risk among African Americans and breast cancer-specific survival generally, however further validation is needed to confirm these findings