Shear and hydrostatic stress regulate fetal heart valve remodeling through YAP-mediated mechanotransduction.

Clinically serious congenital heart valve defects arise from improper growth and remodeling of endocardial cushions into leaflets. Genetic mutations have been extensively studied but explain less than 20% of cases. Mechanical forces generated by beating hearts drive valve development, but how these forces collectively determine valve growth and remodeling remains incompletely understood. Here, we decouple the influence of those forces on valve size and shape, and study the role of YAP pathway in determining the size and shape. The low oscillatory shear stress promotes YAP nuclear translocation in valvular endothelial cells (VEC), while the high unidirectional shear stress restricts YAP in cytoplasm. The hydrostatic compressive stress activated YAP in valvular interstitial cells (VIC), whereas the tensile stress deactivated YAP. YAP activation by small molecules promoted VIC proliferation and increased valve size. Whereas YAP inhibition enhanced the expression of cell-cell adhesions in VEC and affected valve shape. Finally, left atrial ligation was performed in chick embryonic hearts to manipulate the shear and hydrostatic stress in vivo. The restricted flow in the left ventricle induced a globular and hypoplastic left atrioventricular (AV) valves with an inhibited YAP expression. By contrast, the right AV valves with sustained YAP expression grew and elongated normally. This study establishes a simple yet elegant mechanobiological system by which transduction of local stresses regulates valve growth and remodeling. This system guides leaflets to grow into proper sizes and shapes with the ventricular development, without the need of a genetically prescribed timing mechanism.

Changes of gut microbiota between different weight reduction programs.

BACKGROUND: Gut microbiota may induce obesity, diabetes, and metabolic syndrome. Different weight reduction programs may induce different changes in gut microbiota. OBJECTIVES: To assess the changes in gut microbiota between obese adults who participated in 2 different weight reduction programs, the dietary counseling (DC) group and sleeve gastrectomy (SG) group, for 3 months. SETTING: A University Hospital. METHODS: Ten obese participants from each group were matched according to sex, age, and body mass index. Gut microbiota compositions were determined by metagenomics using next-generation sequencing before and after treatment. Anthropometric indices, metabolic factors, and gut microbiota were compared between and within groups. RESULTS: After 3 months of treatment, compared with subjects in DC group, subjects in SG group experienced a greater reduction in body weight, body mass index, body fat, waist and hip circumference, diastolic blood pressure, hemoglobin, insulin, insulin resistance, glutamate pyruvate transaminase, blood urine nitrogen, and glycated hemoglobin (HbA1C). A total of 8, 17, and 46 species experienced significant abundance changes in DC, in SG, and between the 2 groups, respectively. Diversity of the gut flora increased in SG and between the 2 groups after treatment. The weight change over the course of the weight loss program was further adjusted and only 4 species, including Peptoniphilus lacrimalis 315 B, Selenomonas 4 sp., Prevotella 2 sp., and Pseudobutyrivibrio sp., were found to be significantly different between the 2 weight loss programs. These 4 species may be the different gut microbiota change between internal and surgical weight reduction programs. CONCLUSIONS: There are significant differences not only in anthropometric indices and metabolic factors but also in gut microbiota change between the 2 programs.

The prevalence of obesity and metabolic syndrome in Tibetan immigrants living in high altitude areas in Ladakh, India.

OBJECTIVE: To examine the prevalence of obesity and related cardiovascular disease risk factors among Tibetan immigrants living in high altitude areas. RESEARCH METHODS & PROCEDURES: A total of 149 Tibetan immigrants aged 20 years and over were recruited in 2016 in Ladakh, India. Anthropometric indices and biochemical factors were measured. Using the provided Asia-Pacific criteria from the World Health Organization, overweight and obese status were determined. Metabolic syndrome (MetS) was defined according to the American Heart Association. RESULTS: In general, men were older, taller, and had a greater amount of fasting glucose, and uric acid when compared to women. The prevalence of overweight, general obesity, and central obesity was 23.4, 42.6, and 42.6% in men and 7.8, 64.7, and 69.6% in women, respectively. The prevalence of MetS was 10.6% in men and 33.3% in women, respectively. In older subjects, the prevalence of obesity and MetS was found to be greater. In both genders, the prevalence of hypertension, central obesity, and MetS was significantly different among these body mass index (BMI) groups. Compared to the non-central obesity group, the central obesity group has higher weight, BMI, body fat, hip circumference, systolic and diastolic BP, and prevalence of hypertension. No relationship was found between the prevalence of diabetes and fasting glucose and BMI groups or central obesity groups in both genders. CONCLUSIONS: Among this group of Tibetan immigrants living in high altitude areas, women have a higher prevalence of obesity and MetS than men. No relationship was found between diabetes and obesity.