Over a median 9 years of follow-up, 605 (19.4%) participants developed aTRH. Incident aTRH developed among 25.8%, 18.2%, and 15.7% of participants with 0 to 1, 2, and 3 to 5 ideal Life's Simple 7 components, respectively. No participants had 6 or 7 ideal Life's Simple 7 components at baseline. The multivariable adjusted hazard ratios (95% CIs) for incident aTRH associated with 2 and 3 to 5 versus 0 to 1 ideal components were 0.75 (0.61-0.92) and 0.67 (0.54-0.82), respectively. These findings suggest optimizing cardiovascular health may reduce the pill burden and high cardiovascular risk associated with aTRH among individuals with hypertension.Endothelial-to-mesenchymal transition (EndMT) has been shown to contribute to organ fibrogenesis. We have reported that N-acetyl-seryl-aspartyl- lysyl-proline (AcSDKP) restored levels of diabetes mellitus-suppressed FGFR1 (fibroblast growth factor receptor 1), the endothelial receptor essential for combating EndMT. However, the molecular regulation and biological/pathological significance of the AcSDKP-FGFR1 relationship has not been elucidated yet. Here, we demonstrated that endothelial FGFR1 deficiency led to AcSDKP-resistant EndMT and severe fibrosis associated with EndMT-stimulated fibrogenic programming in neighboring cells. Diabetes mellitus induced severe kidney fibrosis in endothelial FGFR1-deficient mice (FGFR1 fl/fl ; VE-cadherin-Cre FGFR1EKO) but not in control mice (FGFR1fl/fl); AcSDKP completely or partially suppressed kidney fibrosis in control or FGFR1EKO mice. Severe fibrosis was also induced in hearts of diabetic FGFR1EKO mice; however, AcSDKP had no effect on heart fibrosis in FGFR1EKO mice. AcSDKP also had no effect on EndMT in either kidney or heart but partially suppressed epithelial-to-mesenchymal transition in kidneys of diabetic FGFR1EKO mice. The medium from FGFR1-deficient endothelial cells stimulated TGFβ (transforming growth factor β)/Smad-dependent epithelial-to-mesenchymal transition in cultured human proximal tubule epithelial cell line, AcSDKP inhibited such epithelial-to-mesenchymal transition. These data demonstrated that endothelial FGFR1 is essential as an antifibrotic core molecule as the target of AcSDKP.Hypertension is a major risk factor for cardiovascular disease and mortality. To identify targets for the prevention of hypertension and its associated disease burden, we used the 2-sample Mendelian randomization method to investigate the causal associations of 18 cardiovascular risk factors and lifestyle behaviors with hypertension. From European-descent genome-wide association studies, we selected genetic variants (P less then 5×10-8) for type 2 diabetes, fasting glucose, lipids, body mass index, smoking, alcohol and coffee consumption, physical activity, sleep duration, insomnia, and educational level. We extracted the genetic associations with hypertension from 2 European cohorts the FinnGen Study (15 870 cases and 74 345 controls) and UK Biobank (54 358 cases and 408 652 controls). The inverse-variance weighted method was used as main analysis method. Genetically predicted triglycerides (pooled odds ratio [OR] per 1 SD, 1.17 [1.10-1.25]), body mass index (OR per 1 SD, 1.42 [1.37-1.48]), alcohol dependence (OR, 1.10 [1.06-1.13]), and insomnia (OR, 1.17 [1.13-1.20]) were associated with a higher odds of hypertension. Mdivi1 Higher genetically predicted high-density lipoprotein cholesterol (OR per 1 SD, 0.88 [0.83-0.94]) and educational level (OR per 1 SD, 0.56 [0.54-0.59]) were associated with a lower odds of hypertension. Suggestive evidence was obtained for type 2 diabetes, smoking initiation and alcohol consumption with a higher hypertension odds, and longer sleep duration with a lower hypertension odds. This Mendelian randomization study identified high-density lipoprotein cholesterol, triglycerides, body mass index, alcohol dependence, insomnia, and educational level as causal risk factors for hypertension. This implicates that these modifiable risk factors are important targets in the prevention of hypertension.The HECT (homologous to the E6-AP carboxyl terminus)-type ubiquitin E3 ligase ITCH is an enzyme that plays an important role in ubiquitin-proteasomal protein degradation. Disheveled proteins (Dvl1 [disheveled protein 1], Dvl2, and Dvl3) are the main components of the Wnt/β-catenin signaling pathway, which is involved in cardiac hypertrophy. The aim of this study was to examine the role of ITCH during development of cardiac hypertrophy. Thoracic transverse aortic constriction (TAC) was performed in transgenic mice with cardiac-specific overexpression of ITCH (ITCH-Tg) and wild-type mice. Cardiac hypertrophy after TAC was attenuated in ITCH-Tg mice, and the survival rate was higher for ITCH-Tg mice than for wild-type mice. Protein interaction between ITCH and Dvls was confirmed with immunoprecipitation in vivo and in vitro. Expression of key molecules of the Wnt/β-catenin signaling pathway (Dvl1, Dvl2, GSK3β [glycogen synthase kinase 3β], and β-catenin) was inhibited in ITCH-Tg mice compared with wild-type mice. Notably, the ubiquitination level of Dvl proteins increased in ITCH-Tg mice. Protein and mRNA expression levels of ITCH increased in response to Wnt3a stimulation in neonatal rat cardiomyocytes. Knockdown of ITCH using small-interfering RNA increased cardiomyocyte size and augmented protein expression levels of Dvl proteins, phospho-GSK3β, and β-catenin after Wnt3a stimulation in cardiomyocytes. Conversely, overexpression of ITCH attenuated cardiomyocyte hypertrophy and decreased protein expression levels of Dvl proteins, phospho-GSK3β and β-catenin. In conclusion, ITCH targets Dvl proteins for ubiquitin-proteasome degradation in cardiomyocytes and attenuates cardiac hypertrophy by suppressing the Wnt/β-catenin signaling pathway.Chronic kidney disease is a global health care burden, yet clinically-proven treatments are limited. Low-intensity shockwave, which utilizes ≈10% of the energy levels used in clinically indicated shockwave lithotripsy, is a promising technique to ameliorate ischemia and regenerate tissues. It has been demonstrated to improve healing in tissues such as bone, muscle, myocardium, and kidney via several mechanisms, particularly through promoting neovascularization. Low-intensity shockwave stimulates mechanoreceptors located primarily in endothelial and proximal tubular cells and subsequently upregulates vascular endothelial growth factors. This, in turn, promotes angiogenesis and ameliorates renal hypoxia, inflammation, and fibrosis, and ultimately preserves renal function. Furthermore, low-intensity shockwave can stimulate release of homing factors to attract endothelial progenitor or stem cells into injured kidneys for tissue repair. These effects may be beneficial in several kidney disease models, including renal artery stenosis, diabetic kidney disease, and various chronic kidney diseases, although most studies reported to date have been performed in animal models.