Honokiol ameliorates angiotensin II-induced hypertension and endothelial dysfunction by inhibiting HDAC6-mediated cystathionine γ-lyase degradation.

Hypertension and endothelial dysfunction are associated with various cardiovascular diseases. Hydrogen sulphide (H2 S) produced by cystathionine γ-lyase (CSE) promotes vascular relaxation and lowers hypertension. Honokiol (HNK), a natural compound in the Magnolia plant, has been shown to retain multifunctional properties such as anti-oxidative and anti-inflammatory activities. However, a potential role of HNK in regulating CSE and hypertension remains largely unknown. Here, we aimed to demonstrate that HNK co-treatment attenuated the vasoconstriction, hypertension and H2 S reduction caused by angiotensin II (AngII), a well-established inducer of hypertension. We previously found that histone deacetylase 6 (HDAC6) mediates AngII-induced deacetylation of CSE, which facilitates its ubiquitination and proteasomal degradation. Our current results indicated that HNK increased endothelial CSE protein levels by enhancing its stability in a sirtuin-3-independent manner. Notably, HNK could increase CSE acetylation levels by inhibiting HDAC6 catalytic activity, thereby blocking the AngII-induced degradative ubiquitination of CSE. CSE acetylation and ubiquitination occurred mainly on the lysine 73 (K73) residue. Conversely, its mutant (K73R) was resistant to both acetylation and ubiquitination, exhibiting higher protein stability than that of wild-type CSE. Collectively, our findings suggested that HNK treatment protects CSE against HDAC6-mediated degradation and may constitute an alternative for preventing endothelial dysfunction and hypertensive disorders.

Cardiovascular disease risk perception among community adults in South China: a latent profile analysis.

Objective: Risk perception, a critical psychological construct, influences health behavior modification and maintenance of individuals with cardiovascular disease (CVD) risk. Little is known about CVD risk perception among Chinese adults. This research examined the profiles of CVD risk perception of community adults in South China, and explored the characteristics and factors that influence their perception of CVD risk. Method: This cross-sectional study was conducted in Hangzhou, Zhejiang Province, in South China from March to July 2022 and included 692 participants. Risk perception was assessed using the Chinese version of the Attitude and Beliefs about Cardiovascular Disease Risk Questionnaire. Latent profile analysis (LPA) was performed to extract latent classes of CVD risk perception. These classes of CVD risk perception were compared with 10-year CVD risk categories to define correctness of estimation. Chi-square tests and multinomial regression analyses were used to identify differences between these categories. Results: Three CVD risk perception classes were identified by LPA: low risk perception (14.2% of participants), moderate risk perception (46.8%), high risk perception (39.0%). Individuals who were aged with 40-60 year (OR = 6.94, 95% CI = 1.86-25.84), diabetes (OR = 6.26, 95% CI = 1.34-29.17), married (OR = 4.52, 95% CI = 2.30-8.90), better subjective health status (OR = 3.23, 95% CI = 1.15-9.10) and perceived benefits and intention to change physical activity (OR = 1.16, 95% CI = 1.05-1.27) were more likely to be in the high-risk perception class. Compared to absolute 10-year CVD risk based on China-PAR, a third of participants (30.1%) correctly estimated their CVD risk, 63.3% overestimated it and 6.6% underestimated it. CVD risk underestimation was associated with hypertension (OR = 3.91, 95% CI = 1.79-8.54), drinking (OR = 3.05, 95% CI = 1.22-7.64), better subjective health status (OR = 2.67, 95% CI = 1.18-6.03). Conclusions: Most adults in South China possess a moderate level of CVD risk perception. Advanced age, higher monthly income, diabetes and better health status were significantly related to higher perceived CVD risk. Individuals with hypertension, drinking and better subjective health status were associated with CVD risk underestimation. Healthcare professionals should pay attention to the indicators for different classes and identify underestimation group as early as possible.

Aerobic Exercise Training Inhibits Neointimal Formation via Reduction of PCSK9 and LOX-1 in Atherosclerosis.

The purpose of this study was to investigate whether aerobic exercise training inhibits atherosclerosis via the reduction of proprotein convertase subtilisin/kexin type 9 (PCSK9) expression in balloon-induced common carotid arteries of a high-fat-diet rats. Male SD (Sprague Dawley) rats fed an eight-weeks high-fat diet were randomly divided into three groups; these were the sham-operated control (SC), the balloon-induced control (BIC) and the balloon-induced exercise (BIE). The aerobic exercise training groups were performed on a treadmill. The major findings were as follows: first, body weight gain was significantly decreased by aerobic exercise training compared to the BIC without change of energy intake. Second, neointimal formation was significantly inhibited by aerobic exercise training in the balloon-induced common carotid arteries of high-fat-diet rats compared to the BIC. Third, low-density lipoprotein (LDL) receptor (LDLr) expression was significantly increased by aerobic exercise training in the livers of the high-fat diet group compared to the BIC, but not the proprotein convertase subtilisin/kexin type 9 (PCSK9) expression. Fourth, aerobic exercise training significantly decreased the expression of PCSK9, the lectin-like oxidized LDL receptor-1 (LOX-1), and vascular cell adhesion molecule-1 (VCAM-1) in balloon-induced common carotid arteries of high-fat-diet rats compared to the BIC. In conclusion, our results suggest that aerobic exercise training increases LDLr in the liver and inhibits neointimal formation via the reduction of PCSK9 and LOX-1 in balloon-induced common carotid arteries of high-fat-diet-induced rats.