Gut microbiota dysbiosis contributes to the development of hypertension.

BACKGROUND: Recently, the potential role of gut microbiome in metabolic diseases has been revealed, especially in cardiovascular diseases. Hypertension is one of the most prevalent cardiovascular diseases worldwide, yet whether gut microbiota dysbiosis participates in the development of hypertension remains largely unknown. To investigate this issue, we carried out comprehensive metagenomic and metabolomic analyses in a cohort of 41 healthy controls, 56 subjects with pre-hypertension, 99 individuals with primary hypertension, and performed fecal microbiota transplantation from patients to germ-free mice. RESULTS: Compared to the healthy controls, we found dramatically decreased microbial richness and diversity, Prevotella-dominated gut enterotype, distinct metagenomic composition with reduced bacteria associated with healthy status and overgrowth of bacteria such as Prevotella and Klebsiella, and disease-linked microbial function in both pre-hypertensive and hypertensive populations. Unexpectedly, the microbiome characteristic in pre-hypertension group was quite similar to that in hypertension. The metabolism changes of host with pre-hypertension or hypertension were identified to be closely linked to gut microbiome dysbiosis. And a disease classifier based on microbiota and metabolites was constructed to discriminate pre-hypertensive and hypertensive individuals from controls accurately. Furthermore, by fecal transplantation from hypertensive human donors to germ-free mice, elevated blood pressure was observed to be transferrable through microbiota, and the direct influence of gut microbiota on blood pressure of the host was demonstrated. CONCLUSIONS: Overall, our results describe a novel causal role of aberrant gut microbiota in contributing to the pathogenesis of hypertension. And the significance of early intervention for pre-hypertension was emphasized.

Burden of hypertension in China over the past decades: Systematic analysis of prevalence, treatment and control of hypertension.

AIMS: To review comprehensively the prevalence, treatment and control of hypertension; and to estimate the burden of hypertension in China, thereby aiding Chinese health policies for better prevention and control of this condition. METHODS AND RESULTS: PubMed, EMbase, China National Knowledge Infrastructure, Wanfang and Chongqing VIP databases were searched for population-based studies published in English and Chinese that described prevalence, treatment and control of hypertension in China, as well as deaths and disabilities attributed to hypertension. All research papers were published between January 1999 and May 2014. Data from 178 studies involving over 2,901,464 participants covering 30 provinces were pooled. Overall, rates of prevalence, treatment and control of hypertension were 28.9%, 35.3% and 13.4% in China. A statistically significant association was observed between temperature gradient and the prevalence of hypertension. There were 10,667 (95% confidence interval 8063-13,345) disability-adjusted life years per 100,000 people. In total, 78.3% of disability-adjusted life years were from years lived with disability and 21.7% from years of life lost due to premature mortality. CONCLUSIONS: Although there has been a slight improvement in rates for the treatment and control of hypertension, these rates were still suboptimal, especially for men and people living in rural areas. Low and middle-income provinces had a comparatively huge burden of hypertension, which is a considerable risk factor for reducing life expectancy. Our analysis may be helpful in generating a current overview of hypertension in China.

Alcohol Regulates Genes that Are Associated with Response to Endocrine Therapy and Attenuates the Actions of Tamoxifen in Breast Cancer Cells.

Hereditary, hormonal, and behavioral factors contribute to the development of breast cancer. Alcohol consumption is a modifiable behavior that is linked to increased breast cancer risks and is associated with the development of hormone-dependent breast cancers as well as disease progression and recurrence following endocrine treatment. In this study we examined the molecular mechanisms of action of alcohol by applying molecular, genetic, and genomic approaches in characterizing its effects on estrogen receptor (ER)-positive breast cancer cells. Treatments with alcohol promoted cell proliferation, increased growth factor signaling, and up-regulated the transcription of the ER target gene GREB1 but not the canonical target TFF1/pS2. Microarray analysis following alcohol treatment identified a large number of alcohol-responsive genes, including those which function in apoptotic and cell proliferation pathways. Furthermore, expression profiles of the responsive gene sets in tumors were strongly associated with clinical outcomes in patients who received endocrine therapy. Correspondingly, alcohol treatment attenuated the anti-proliferative effects of the endocrine therapeutic drug tamoxifen in ER-positive breast cancer cells. To determine the contribution and functions of responsive genes, their differential expression in tumors were assessed between outcome groups. The proto-oncogene BRAF was identified as a novel alcohol- and estrogen-induced gene that showed higher expression in patients with poor outcomes. Knock-down of BRAF, moreover, prevented the proliferation of breast cancer cells. These findings not only highlight the mechanistic basis of the effects of alcohol on breast cancer cells and increased risks for disease incidents and recurrence, but may facilitate the discovery and characterization of novel oncogenic pathways and markers in breast cancer research and therapeutics.