ASH2L Deficiency in Smooth Muscle Drives Pulmonary Vascular Remodeling.

Background: Histone H3 lysine 4 methylation is one of the most abundant epigenetic modifications, which has been recently linked to vascular remodeling in pulmonary hypertension (PH). SET1/MLL methyltransferase complexes comprise the main enzymes responsible for methylating H3 lysine 4, yet their roles in vascular remodeling and PH are not fully understood. We aim to assess the contribution of ASH2L, a core SET1/MLL family member, to the pathogenesis of PH.

Imbalance and dysfunction of transient receptor potential channels contribute to the pathogenesis of hypertension.

Intracellular Ca(2+) homeostasis is essential for vascular function and blood pressure regulation. Because of their unique roles in regulating intracellular Ca(2+) concentration and vascular function, a novel class of non-selective cation channels, called transient receptor potential (TRP) channels, have emerged at the frontier of hypertension research. Based on their role in vasculature function regulation, TRP channels can be divided into two functional subtypes: one that participates in vasoconstriction and one that participates in vasodilatation.

[Activation of transient receptor potential vanilloid 1 inhibits RhoA/Rho kinase and improves vasorelaxation dysfunction mediated by high-fat diet in mice].

Objective: To investigate the role of dietary capsaicin in activating transient receptor potential vanilloid 1 (TRPV1) and thus influencing the vascular dysfunction mediated by high-fat diet and the potential mechanisms.

Methods: A total of 80 male C57BL/6J mice aged 10 weeks were equally divided into four groups, in which the mice were fed with normal diet (ND), normal diet plus capsaicin (NC), high-fat diet (HD), or high-fat diet plus capsaicin (HC) for 20 weeks. Tail-cuff blood pressure (BP), vascular function of mice aortic rings, expressions of voltage-gated potassium-channel Kv1.

[Relationship of different types of abdominal obesity to risk of metabolic syndrome].

Objective: To explore the relationship of different types of abdominal obesity to risk of metabolic syndrome (MS).

Methods: Visceral fat area (VA) and substantial fat area (SA) were assessed by CT in 846 patients, 470 males and 376 females, aged 55 +/- 12, who suffered from at least one cardiometabolic risk factor and divided into 4 groups according to their VA and waist circumference (WC): non-obesity, masked visceral fat obesity (VFO), pseudo-VFO, and VFO groups. Blood pressure, fasting blood glucose, fasting serum insulin, and lipid profile were also measured.

Association of transient receptor potential canonical type 3 (TRPC3) channel transcripts with proinflammatory cytokines.

We investigated whether expression of non-selective cation channels of the transient receptor potential canonical (TRPC) channel family are associated with proinflammatory cytokines in monocytes. Using quantitative RT-PCR we studied the expression of TRPC3, interleukin-1beta (IL-1beta), and tumor necrosis factor-alpha (TNF-alpha) in monocytes from 15 patients with essential hypertension and 16 age- and sex-matched normotensive control subjects. We observed an approximately 8-fold increase of TRPC3 transcripts in monocytes from patients with essential hypertension compared to normotensive control subjects (p<0.

Monocytes from spontaneously hypertensive rats show increased store-operated and second messenger-operated calcium influx mediated by transient receptor potential canonical Type 3 channels.

Background: We recently showed that increased expression of the transient receptor potential canonical Type 3 (TRPC3) channel is associated with genetic hypertension. It is unknown whether store-operated TRPC3 channels, which are activated after depletion of intracellular stores, or second messenger-operated TRPC3 channels, which are activated by 1-oleoyl-2-acetyl-sn-glycerol, show augmented responses in monocytes in genetic hypertension and support the development of vascular disease.

Methods: Using the fluorescent-dye technique, we studied store-depleted and thapsigargin-induced, store-operated calcium influx and 1-oleoyl-2-acetyl-sn-glycerol-induced second messenger-operated calcium influx into monocytes from spontaneously hypertensive rats (SHRs) and from normotensive Wistar-Kyoto rats (WKYs).

[Relationship between abdominal obesity and left ventricular weight/function].

Objective: To observe the relationship between abdominal obesity and left ventricular weight/function.

Methods: A total of 495 patients [265 males, mean age (55 +/- 12) years] with hypertension (139), diabetes (65), metabolic syndrome (285), diabetes complicated with hypertension (11) were enrolled in this study. Visceral adipose area (VA), the subcutaneous adipose (SA), the total abdominal adipose (TA) were measured by computerized tomography (CT) and left ventricular weight and function were obtained by echocardiography.

Increased store-operated and 1-oleoyl-2-acetyl-sn-glycerol-induced calcium influx in monocytes is mediated by transient receptor potential canonical channels in human essential hypertension.

Objective: Activation of nonselective cation channels of the transient receptor potential canonical (TRPC) family has been associated with hypertension. Whether store-operated channels, which are activated after depletion of intracellular stores, or second-messenger-operated channels, which are activated by 1-oleoyl-2-acetyl-sn-glycerol, are affected in essential hypertension is presently unknown.

Methods: Using a polymerase chain reaction, an in-cell western assay and the fluorescent dye technique we studied TRPC3, TRPC5, and TRPC6 expression and store-operated and 1-oleoyl-2-acetyl-sn-glycerol-induced calcium influx into human monocytes in 19 patients with essential hypertension and in 17 age-matched and sex-matched normotensive control individuals.

Activation of transient receptor potential vanilloid type-1 channel prevents adipogenesis and obesity.

We tested the hypothesis that activation of transient receptor potential vanilloid type-1 (TRPV1) by capsaicin prevents adipogenesis. TRPV1 channels in 3T3-L1-preadipocytes and visceral adipose tissue from mice and humans were detected by immunoblotting and quantitative real-time RT-PCR. The effect of TRPV1 on cytosolic calcium was determined fluorometrically in 3T3-L1-preadipocytes and in human visceral fat tissue.

[Renin-angiotensin system in mesenteric adipose tissues in rats with metabolic syndrome].

Objective: To investigate the renin-angiotensin system (RAS) in mesenteric adipose tissues and effect of angiotensin II on adipocyte differentiation.

Methods: Thirty normal 8-week-old male Wistar rats were divided into groups on normal diet and high-fat diet. The rats on high-fat diet for 24 weeks developed the metabolic syndrome respectively.

Exercise reduces adipose tissue via cannabinoid receptor type 1 which is regulated by peroxisome proliferator-activated receptor-delta.

Obesity is one major cardiovascular risk factor. We tested effects of endurance exercise on cannabinoid receptor type 1 (CB1) and peroxisome proliferator-activated receptor-delta (PPAR-delta)-dependent pathways in adipose tissue. Male Wistar rats were randomly assigned to standard laboratory chow or a high-fat diet without and with regular endurance exercise.