Catheter-based adrenal ablation: an alternative therapy for patients with aldosterone-producing adenoma.

Unilateral adrenalectomy is the standard treatment for patients with aldosterone-producing adenoma (APA), but it lacks an option for patients with APA who refuse or are not suitable for surgery. In this study, we studied whether catheter-based adrenal ablation for APA is comparable to adrenalectomy. A total of 2185 hypertensive patients were screened, and 112 patients with APA were recruited and counselled on the treatment options. Fifty-two patients opted for catheter-based adrenal ablation, and 60 opted for adrenalectomy. Clinical and biochemical outcomes were assessed at 6 months after treatment. Factors associated with hypertension remission and the advantages and limitations of this approach were evaluated. According to the primary aldosteronism surgical outcome (PASO) criteria, complete and partial clinical success was achieved in 21 (40.4%) and 23 (44.2%) patients in the ablation group vs. 33 (55.0%) and 23 (38.3%) patients in the adrenalectomy group, respectively. Complete and partial biochemical success was achieved in 30 (57.7%) and 17 (32.7%) patients in the ablation group vs. 51 (85.0%) and 5 (8.3%) patients in the adrenalectomy group, respectively. The complete clinical success rate was not (P > 0.05), but the complete biochemical success rate was significantly different between the two groups (P < 0.01). Factors associated with adrenal ablation-mediated hypertension remission were hypertension duration and serum potassium level at baseline. Compared with surgery, adrenal ablation requires a shorter operating time and time to resume physical activity. Catheter-based adrenal ablation may be an alternative and feasible option for APA patients unwilling to receive surgical treatment.

Clinical Characteristics of Target Organ Damage in Primary Aldosteronism with or without Metabolic Syndrome.

The aim of this study is to investigate the prevalence of metabolic disorders in patients with primary aldosteronism (PA) and target organ damage (TOD) in different subtypes of patients with PA with or without metabolic syndrome (MS). Patients with PA were screened out from those with secondary hypertension and then subtyped via adrenal venous sampling (AVS). Baseline clinical characteristics (blood pressure, blood glucose, abdominal circumference, and lipid profile) were collected for the diagnosis of MS. Organ damage was evaluated according to cardiac and carotid ultrasound and urine microalbumin measurements. In all 261 patients with PA, 113 patients had concomitant MS and experienced more severe cardiac hypertrophy and increased intima-media thickness (IMT). The incidence of MS and diabetes mellitus (DM) had no statistic difference between the two groups, moreover, the rates of TOD were not different except microalbuminuria. However, metabolic disorders caused more remarkable TOD in PA patients with unilateral hypersecretion. It showed that cardiac hypertrophy was associated with obesity while microalbuminuria was related to plasma aldosterone concentration (PAC) in PA patients. In this retrospective study, our findings suggest that the effect of metabolic disorders on organ damage is more remarkable in patients with unilateral PA.

Assessment of sublingual microcirculation for the screening of diabetic nephropathy.

OBJECTIVE: To investigate the potential of employing sublingual microcirculation as an early noninvasive screening technique for diabetic nephropathy (DN). RESEARCH DESIGN AND METHODS: We recruited 89 patients with type 2 diabetes mellitus (T2DM) and 41 healthy subjects in this cross-sectional observational study. All participants underwent fluorescein fundus angiography, vibration perception testing, 10 g (Semmes-Weinstein) monofilament examination, nerve conduction velocity, and 24-h urine microalbumin determination. HbA1c, fasting plasma glucose, blood lipid, and estimated glomerular filtration rate(eGFR) were measured. Sublingual microcirculatory images were captured using side-stream dark-field (SDF) microcirculation microscopy, and total and perfused vascular density (TVD and PVD) were calculated. RESULTS: The sublingual microcirculatory parameters denoting microvascular density and perfusion were negatively correlated with both fasting plasma glucose (TVD, r = - 0.316, P < 0.001; PVD, r = - 0.350, P < 0.001; PPV, r = - 0.279, P = 0.001) and HbA1c (TVD, r = - 0.367, P < 0.001; PVD, r = - 0.423, P < 0.001; PPV, r = - 0.399, P < 0.001). Diabetes patients already had a reduction in sublingual microcirculation compared with healthy control, and more severe reductions in TVD (7.07 ± 1.64 vs. 9.67 ± 1.94 mm/mm2, P < 0.001) and PVD (5.88 ± 1.82 vs. 8.64 ± 2.46 mm/mm2, P < 0.001) were found in those diabetes patients developed microvascular complications. Sublingual microcirculation impairment was accompanied with higher urinary albumin creatinine ratio (UACR). Receiver operating characteristic (ROC) analysis showed that TVD (area under the curve, AUC = 0.890 [0.836 0.944], P < 0.001) and PVD (AUC = 0.883 [0.826, 0.940], P < 0.001) could be indicators for DN screening. We derived a combined predictor index (CPI) considering both TVD and PVD for screening DN, and both the AUC (0.892, [0.838 0.945], P < 0.001) and cutoff point of 11.30 mm/mm2 showed great improvement (sensitivity: 95.5%, specificity: 67.4%). CONCLUSIONS: Diabetes patients experienced impaired sublingual microcirculation, which was closely correlated with UACR. Sublingual microcirculation monitoring could be used for the noninvasive early detection of DN.

Activation of Glucagon-Like Peptide-1 Receptor Ameliorates Cognitive Decline in Type 2 Diabetes Mellitus Through a Metabolism-Independent Pathway.

Background Patients with hypertension and diabetes mellitus are susceptible to dementia, but regular therapy fails to reduce the risk of dementia. Glucagon-like peptide-1 receptor agonists have neuroprotective effects in experimental studies. We aimed to assess the effect of liraglutide, a glucagon-like peptide-1 receptor agonist, on cognitive function and whether its effect was associated with metabolic changes in patients with type 2 diabetes mellitus. Methods and Results Fifty patients with type 2 diabetes mellitus were recruited in this prospective study. All patients underwent cognitive assessment and brain activation monitoring by functional near-infrared spectroscopy. At 12 weeks, patients in the glucagon-like peptide-1 group acquired better scores in all cognitive tests and showed remarkable improvement in memory and attention (P=0.040) test compared with the control group after multivariable adjustment. Compared with the control group, liraglutide significantly increased activation of the dorsolateral prefrontal cortex and orbitofrontal cortex brain regions (P=0.0038). After liraglutide treatment, cognitive scores were significantly correlated with changes in these activating brain regions (P<0.05), but no correlation was observed between the changes in cognitive function and changes of body mass index, blood pressure, and glycemic levels. Conclusions We concluded that liraglutide improves cognitive decline in patients with type 2 diabetes mellitus. This beneficial effect is independent of its hypoglycemic effect and weight loss. The optimal intervention should be targeted to cognitive decline in the early stages of dementia. Registration URL: https://www.ClinicalTrials.gov; Unique identifier: NCT03707171.

Achieving blood pressure targets and antihypertensive effects through metabolic surgery in type 2 diabetes patients with hypertension.

AIMS: The effect of metabolic surgery compared with that of conventional therapy on target blood pressure (BP)and defined daily dose (DDD) of antihypertensive drugs in type 2 diabetes (T2DM) patients with hypertension remains unclear. This study aimed to investigate the differences in target BP and DDD between metabolic surgery and conventional treatment in T2DM patients with hypertension. MATERIALS AND METHODS: This was a prospective study of 535 diabetes patients who underwent metabolic surgery (n = 112) and medical treatment (n = 423). Changes in the target BP from baseline to every follow-up were analysed. RESULTS: Metabolic surgery decreased both office systolic and diastolic BP (DBP) and also significantly reduced ambulatory systolic BP (SBP; 132 ± 2 vs. 119 ± 1 mmHg, p < 0.0001), but not DBP (78 ± 1 vs. 76 ± 1 mmHg, p = 0.177). Patients maintained their SBP at <120 mmHg after 2 years (50% vs. 1.9%, p < 0.0001). Moreover, the rate of achieving the target SBP of 130 and 140 mmHg was also significantly higher in the surgery group, and this started from the initial 6 months after commencing treatment to the end of follow-up. The dosage (DDD: 1.44 ± 0.65 vs. 0.32 ± 0.05, p < 0.001) of antihypertensive medication was significantly decreased after metabolic surgery. Furthermore, metabolic surgery, but not medical treatment, markedly improved the risks of atherosclerotic cardiovascular disease. CONCLUSIONS: Metabolic surgery can effectively achieve the BP target and reduce the usage of antihypertensive medications as well as improve multiple metabolic dysfunction in T2DM patients with hypertension. This study provides an alternative approach to antagonize the metabolic related hypertension.

Low-glucose-sensitive TRPC6 dysfunction drives hypoglycemia-induced cognitive impairment in diabetes.

BACKGROUND: Recurrent moderate hypoglycemia (RH), a major adverse effect of hypoglycemic therapy in diabetic patients, is one of the main risk factors for cognitive impairment and dementia. Transient receptor potential canonical channel 6 (TRPC6) is a potential therapeutic target for Alzheimer's disease (AD) and its expression is highly regulated by glucose concentration. OBJECTIVE: To investigate whether RH regulates the expression of TRPC6 in brain and whether TRPC6 dysfunction can drive hypoglycemia-associated cognitive impairment in diabetes, and reveal the underlying mechanism. METHODS: Histological staining, in vivo two-photon Ca2+ imaging, and behavioral tests were used to measure neuronal death, brain network activity, and cognitive function in mice, respectively. High-resolution respirometry and transmission electron microscope were used to assess mitochondrial structure and function. Intracellular calcium measurement and molecular biology techniques were conducted to uncover the underlying mechanism. RESULTS: Here, we report that the expression of TRPC6 in hippocampus was specifically repressed by RH in streptozocin-induced type 1 diabetic mice, but not in nondiabetic mice. TRPC6 knockout directly leads to neuron loss, neuronal activity, and cognitive function impairment under diabetic condition, the degree of which is similar to that of RH. Activation of TRPC6 with hyperforin substantially improved RH-induced cognitive impairment. Mechanistically, TRPC6 inhibited mitochondrial fission in the hippocampus of diabetic mice undergoing RH episodes by activating adenosine 5'-monophosphate-activated protein kinase, and TRPC6-mediated cytosolic calcium influx was required for this process. Clinically, dysfunction of TRPC6 was closely associated with cognitive impairment in type 2 diabetic patients with RH. CONCLUSIONS: Our results indicate that TRPC6 is a critical sensitive cation channel to hypoglycemia and is a promising target to prevent RH-induced cognitive impairment by properly orchestrating the mitochondrial dynamics in diabetic patients.

Adrenal artery ablation for primary aldosteronism without apparent aldosteronoma: An efficacy and safety, proof-of-principle trial.

Primary aldosteronism (PA) is associated with resistant hypertension and cardiovascular events. There are some limitations of current medical and surgical therapies for PA. To determine the efficacy and safety of catheter-based adrenal artery ablation for treatment of PA patients who refused both surgery and medical therapy, we performed this prospective cohort study. Thirty-six PA patients without apparent aldosteronoma were treated by adrenal artery ablation. Primary outcome was postoperative blood pressure and defined daily dose (DDD) of antihypertensive medications after adrenal ablation. Secondary outcome was biochemical success. We assessed outcomes based on Primary Aldosteronism Surgical Outcome (PASO) criteria. Adrenal CT scan, biochemical evaluation, adrenal artery ablation and adrenal venous sampling (AVS) were underwent. After adrenal ablation, complete clinical success (normotension without antihypertensive medication) was achieved in 9/36 (25.0%) patients and partial clinical success (reduction in blood pressure or less antihypertensive medication) in 13/36 (36.1%) patients. Complete biochemical success (correction of hypokalemia and normalization of aldosterone-to-renin ratio) was achieved in 16/36 (44.4%) patients. Office-based and ambulatory blood pressures were reduced by 17/7 and 11/2 mmHg at 6 months after ablation, respectively. The plasma cortisol level in the ablation group decreased slightly, but no patient developed hypoadrenocorticism. Catheter-based adrenal ablation appears to produce substantial and sustained blood pressure reduction and biochemical improvement, with only minor adverse events in PA patients without apparent aldosteronoma. This therapy could be an important supplement for current PA treatments.

Detrimental Effect of C-Reactive Protein on the Cardiometabolic Cells and Its Rectifying by Metabolic Surgery in Obese Diabetic Patients.

BACKGROUND: High-sensitivity C-reactive protein (hs-CRP) has been regarded as a biomarker of low-degree inflammation in illness; however, whether CRP exerts its pathogenic effect on the cardiometabolic system remains unknown. Aside from the beneficial effects of metabolic surgery on cardiometabolic system, its impact on inflammation still worth examining. Thus, this study aims to investigate the effect of CRP on adipose and vascular cells, and their responses to metabolic surgery in obese diabetic patients. PATIENTS AND METHODS: The expression of CRP and RAS- and ERK-related factors in the adipocytes and VSMCs were measured. Obese patients with type 2 diabetes who underwent metabolic surgery were followed up for 2 years thereafter. Laboratory tests, which included serum hs-CRP levels and visceral fat thickness (VFT), were obtained before and after surgery. RESULTS: CRP administration significantly and dose-dependently increased the intracellular-free calcium concentration ([Ca2+]i) in cultured adipocytes and in the VSMCs. CRP administration significantly increased ACE, Ang II, AT1R and p-ERK expressions, but reduced ACE2 expression in both the adipocytes and VSMCs. Clinical study showed that VFT was closely associated with serum hs-CRP. Furthermore, VFT and serum hs-CRP were found to be highly associated with blood pressure. Finally, metabolic surgery remarkably decreased blood pressure, visceral fat and serum hs-CRP levels. CONCLUSION: CRP has a detrimental effect on cardiometabolic cells, aside from functioning merely as a biomarker. Serum hs-CRP levels are highly associated with hypertension and visceral obesity, which can be antagonized by metabolic surgery in obese diabetic patients.

High-salt intake increases TRPC3 expression and enhances TRPC3-mediated calcium influx and systolic blood pressure in hypertensive patients.

Enhanced transient receptor potential canonical subtype 3 (TRPC3) expression and TRPC3-mediated calcium influx in monocytes from hypertensive rats and patients are associated with increased blood pressure. Daily salt intake is closely related to hypertension, but the relationship between TRPC3 expression and salt intake has not yet been evaluated in hypertensive patients. Using reverse transcription-polymerase chain reaction, we studied the expression of TRPC3 and TRPC3-related store-operated calcium entry (SOCE) in peripheral blood mononuclear cells (PBMCs) from hypertensive and normotensive control subjects. Measurement of SOCE was performed using the fluorescent dye Fura-2 AM. Participants were divided into a low-salt group (<9 g) and a high-salt group (≥9 g) based on 24-h urinary sodium excretion. Increased TRPC3 mRNA expression levels and SOCE were observed in THP-1 cells after high-NaCl treatment. However, administration of the TRPC3-specific inhibitor Pyr3 significantly decreased the effect. Furthermore, the TRPC3 mRNA expression levels in PBMCs from high-salt intake patients with essential hypertension were significantly higher than those in low-salt intake patients compared with those in normotensive control subjects. We also observed significantly increased TRPC3-mediated SOCE in PBMCs from hypertensive subjects (but not from normotensive control subjects), with calcium concentration correlating with salt intake. More importantly, TRPC3 mRNA levels showed a significant correlation with salt intake and systolic blood pressure in patients with essential hypertension. This study demonstrated, for the first time, that increased TRPC3 mRNA levels are associated with elevated salt intake and systolic blood pressure in hypertensive patients.

Statin therapy improved long-term prognosis in patients with major non-cardiac vascular surgeries: a systematic review and meta-analysis.

OBJECTIVE: To investigate whether statin intervention will improve the long-term prognosis of patients undergoing major non-cardiac vascular surgeries. METHODS: Major database searches for clinical trials enrolling patients undergoing major non-cardiac vascular surgeries, including lower limb revascularization, carotid artery surgeries, arteriovenous fistula, and aortic surgeries, were performed. Subgroup analyses, stratified by surgical types or study types, were employed to obtain statistical results regarding survival, patency rates, amputation, and cardiovascular and stroke events. Odds ratio (ORs) and 95% confidence intervals (CIs) were calculated by Review Manager 5.3. Sensitivity analysis, publication bias and meta-regression were conducted by Stata 14.0. RESULTS: In total, 34 observational studies, 8 prospective cohort studies and 4 randomized controlled clinical trials (RCTs) were enrolled in the present analysis. It was demonstrated that statin usage improved all-cause mortality in lower limb, carotid, aortic and mixed types of vascular surgery subgroups compared with those in which statins were not used. Additionally, the employment of statins efficiently enhanced the primary and secondary patency rates and significantly decreased the amputation rates in the lower limb revascularization subgroup. Furthermore, for other complications, statin intervention decreased cardiovascular events in mixed types of vascular surgeries and stroke incidence in the carotid surgery subgroup. No significant publication bias was observed. The meta-regression results showed that the morbidity of cardiovascular disease or the use of aspirin might affect the overall estimates in several subgroups. CONCLUSIONS: This meta-analysis demonstrated that statin therapy was associated with improved survival rates and patency rates and with reduced cardiovascular or stroke morbidities in patients who underwent non-cardiac vascular surgeries.

Enjoyment of Spicy Flavor Enhances Central Salty-Taste Perception and Reduces Salt Intake and Blood Pressure.

High salt intake is a major risk factor for hypertension and is associated with cardiovascular events. Most countries exhibit a traditionally high salt intake; thus, identification of an optimal strategy for salt reduction at the population level may have a major impact on public health. In this multicenter, random-order, double-blind observational and interventional study, subjects with a high spice preference had a lower salt intake and blood pressure than subjects who disliked spicy food. The enjoyment of spicy flavor enhanced salt sensitivity and reduced salt preference. Salt intake and salt preference were related to the regional metabolic activity in the insula and orbitofrontal cortex (OFC) of participants. Administration of capsaicin-the major spicy component of chili pepper-enhanced the insula and OFC metabolic activity in response to high-salt stimuli, which reversed the salt intensity-dependent differences in the metabolism of the insula and OFC. In animal study, OFC activity was closely associated with salt preference, and salty-taste information processed in the OFC was affected in the presence of capsaicin. Thus, interventions related to this region may alter the salt preference in mice through fiber fluorometry and optogenetic techniques. In conclusion, enjoyment of spicy foods may significantly reduce individual salt preference, daily salt intake, and blood pressure by modifying the neural processing of salty taste in the brain. Application of spicy flavor may be a promising behavioral intervention for reducing high salt intake and blood pressure.

A novel use of hill function and utility of 99mTc-MIBI scintigraphy to detect earlier lower extremity microvascular perfusion in patients with type 2 diabetes.

We use the Hill function to analyze the dynamics of Tc-99m 2 methoxy-isobutyl-isonitrile (Tc-MIBI) scintigraphy data and to examine the earlier lower extremity microvascular perfusion of diabetic patients without typical clinical symptoms and with the preserved normal ankle-brachial index (ABI).Eighty-eight participants (30 healthy control, 34 diabetic patients, and 24 diabetic patients with peripheral arterial disease [PAD]) were recruited and applied Tc-MIBI scintigraphy. Fourteen diabetic patients with PAD also underwent computed tomography angiography (CTA) examination and were performed endovascular interventions.Diabetic patients with normal ABI already have significantly impaired maximum Tc-MIBI muscle perfusion counts (P < .001) and the peak times of the lower extremity muscle perfusion (P < .05). Tc-MIBI scintigraphy showed great consistent with ABI and CTA in detecting PAD. Tc-MIBI scintigraphy was also found to be effective in evaluating lower extremity circulation after endovascular interventions (P < .05).Hill function-based analysis of Tc-MIBI scintigraphy might be effective method to evaluate earlier lower extremity perfusion changes in diabetic patients.

Activation of Transient Receptor Potential Melastatin Subtype 8 Attenuates Cold-Induced Hypertension Through Ameliorating Vascular Mitochondrial Dysfunction.

BACKGROUND: Environmental cold-induced hypertension is common, but how to treat cold-induced hypertension remains an obstacle. Transient receptor potential melastatin subtype 8 (TRPM8) is a mild cold-sensing nonselective cation channel that is activated by menthol. Little is known about the effect of TRPM8 activation by menthol on mitochondrial Ca2+ homeostasis and the vascular function in cold-induced hypertension. METHODS AND RESULTS: Primary vascular smooth muscle cells from wild-type or Trpm8-/- mice were cultured. In vitro, we confirmed that sarcoplasmic reticulum-resident TRPM8 participated in the regulation of cellular and mitochondrial Ca2+ homeostasis in the vascular smooth muscle cells. TRPM8 activation by menthol antagonized angiotensin II induced mitochondrial respiratory dysfunction and excess reactive oxygen species generation by preserving pyruvate dehydrogenase activity, which hindered reactive oxygen species-triggered Ca2+ influx and the activation of RhoA/Rho kinase pathway. In vivo, long-term noxious cold stimulation dramatically increased vasoconstriction and blood pressure. The activation of TRPM8 by dietary menthol inhibited vascular reactive oxygen species generation, vasoconstriction, and lowered blood pressure through attenuating excessive mitochondrial reactive oxygen species mediated the activation of RhoA/Rho kinase in a TRPM8-dependent manner. These effects of menthol were further validated in angiotensin II-induced hypertensive mice. CONCLUSIONS: Long-term dietary menthol treatment targeting and preserving mitochondrial function may represent a nonpharmaceutical measure for environmental noxious cold-induced hypertension.

Taurine Supplementation Lowers Blood Pressure and Improves Vascular Function in Prehypertension: Randomized, Double-Blind, Placebo-Controlled Study.

Taurine, the most abundant, semiessential, sulfur-containing amino acid, is well known to lower blood pressure (BP) in hypertensive animal models. However, no rigorous clinical trial has validated whether this beneficial effect of taurine occurs in human hypertension or prehypertension, a key stage in the development of hypertension. In this randomized, double-blind, placebo-controlled study, we assessed the effects of taurine intervention on BP and vascular function in prehypertension. We randomly assigned 120 eligible prehypertensive individuals to receive either taurine supplementation (1.6 g per day) or a placebo for 12 weeks. Taurine supplementation significantly decreased the clinic and 24-hour ambulatory BPs, especially in those with high-normal BP. Mean clinic systolic BP reduction for taurine/placebo was 7.2/2.6 mm Hg, and diastolic BP was 4.7/1.3 mm Hg. Mean ambulatory systolic BP reduction for taurine/placebo was 3.8/0.3 mm Hg, and diastolic BP was 3.5/0.6 mm Hg. In addition, taurine supplementation significantly improved endothelium-dependent and endothelium-independent vasodilation and increased plasma H2S and taurine concentrations. Furthermore, changes in BP were negatively correlated with both the plasma H2S and taurine levels in taurine-treated prehypertensive individuals. To further elucidate the hypotensive mechanism, experimental studies were performed both in vivo and in vitro. The results showed that taurine treatment upregulated the expression of hydrogen sulfide-synthesizing enzymes and reduced agonist-induced vascular reactivity through the inhibition of transient receptor potential channel subtype 3-mediated calcium influx in human and mouse mesenteric arteries. In conclusion, the antihypertensive effect of chronic taurine supplementation shows promise in the treatment of prehypertension through improvement of vascular function.

Enhanced Store-Operated Calcium Entry in Platelets is Associated with Peripheral Artery Disease in Type 2 Diabetes.

BACKGROUND/AIMS: Platelet dysfunction plays an important role in thrombosis in diabetes with peripheral artery disease (PAD). Store-operated calcium entry (SOCE) and stromal interaction molecule 1 (STIM1) regulate platelet activity by modulating calcium influx. We hypothesized that enhanced SOCE in platelets is associated with diabetes with PAD. METHODS: We studied the activity of platelets from healthy participants and from type 2 diabetic patients. Platelet calcium influx and protein expression of STIM1 and sarcoendoplasmic reticulum Ca2+-ATPase 3 (SERCA3) were investigated. RESULTS: Compared with platelets from diabetic patients without PAD, platelets from diabetic patients with PAD exhibited significantly increased SOCE . Menthol administration completely inhibited calcium influx in platelets from diabetic patients without PAD, but this effect was blunted in those from diabetic patients with PAD. Furthermore, the increase in SOCE was correlated with the ankle brachial index (ABI) in diabetic patients. High glucose significantly up-regulated STIM1 and SERCA3 protein expression and induced the phosphorylation of phospholipase C (PLC) in platelets from healthy participants. This effect was attenuated in the presence of menthol or U73122, an inhibitor of PLC. Similarly, significant increases in STIM1 and SERCA3 protein expression were found in platelets from diabetic patients compared to those from healthy participants. CONCLUSION: Platelets from diabetic patients with PAD exhibited enhanced Store-operated calcium influx, which was associated with elevated STIM1/SERCA3 expression via a PLC-dependent pathway and was inhibited by menthol.

Mitochondrial respiratory dysfunctions of blood mononuclear cells link with cardiac disturbance in patients with early-stage heart failure.

Patients with cardiometabolic risk factors and asymptomatic cardiac hypertrophy are hallmarks of early-stage heart failure (HF). We hypothesized that mitochondrial respiratory dysfunctions of peripheral blood mononuclear cells (PBMCs) may be associated with inflammation and oxidative stress in early-stage HF patients complicated with cardiometabolic risk factors. Totally 49 subjects were enrolled with 25 early-stage HF patients (stages A and B) having cardiac hypertrophy and dysfunction and 24 healthy controls. It showed that excessive inflammation and reduced antioxidant capacity were closely associated with cardiac abnormalities in early-stage HF patients. Furthermore, the values of mitochondrial respiratory functional parameters R, CIOXPHOS, CIIOXPHOS, CI+IIOXPHOS, CI+IIETS and CIIETS were significantly lowered in early-stage HF patients. Interestingly, these respiratory parameters were correlated with inflammation and antioxidant capacity in participants. Finally, cardiometabolic risk factors such as salt intake and blood pressure were related to the mitochondrial respiratory dysfunctions, which were further validated by in vitro experiments. Our study indicated that cardiometabolic risk factor-mediated mitochondrial respiratory dysfunctions of PBMCs link with the cellular inflammation / oxidative stress and cardiac disturbance in early-stage HF.

Activation of TRPV1 channel by dietary capsaicin improves visceral fat remodeling through connexin43-mediated Ca2+ influx.

BACKGROUND: The prevalence of obesity has dramatically increased worldwide and has attracted rising attention, but the mechanism is still unclear. Previous studies revealed that transient receptor potential vanilloid 1 (TRPV1) channels take part in weight loss by enhancing intracellular Ca2+ levels. However, the potential mechanism of the effect of dietary capsaicin on obesity is not completely understood. Ca2+ transfer induced by connexin43 (Cx43) molecules between coupled cells takes part in adipocyte differentiation. Whether TRPV1-evoked alterations in Cx43-mediated adipocyte-to-adipocyte communication play a role in obesity is unknown. MATERIALS AND METHODS: We investigated whether Cx43 participated in TRPV1-mediated adipocyte lipolysis in cultured 3T3-L1 preadipocytes and visceral adipose tissues from humans and wild-type (WT) and TRPV1-deficient (TRPV1-/-) mice. RESULTS: TRPV1 and Cx43 co-expressed in mesenteric adipose tissue. TRPV1 activation by capsaicin increased the influx of Ca2+ in 3T3-L1 preadipocytes and promoted cell lipolysis, as shown by Oil-red O staining. These effects were deficient when capsazepine, a TRPV1 antagonist, and 18 alpha-glycyrrhetinic acid (18α-GA), a gap-junction inhibitor, were administered. Long-term chronic dietary capsaicin reduced the weights of perirenal, mesenteric and testicular adipose tissues in WT mice fed a high-fat diet. Capsaicin increased the expression levels of p-CaM, Cx43, CaMKII, PPARδ and HSL in mesenteric adipose tissues from WT mice fed a high-fat diet, db/db mice, as well as obese humans, but these effects of capsaicin were absent in TRPV1-/- mice. Long-term chronic dietary capsaicin decreased the body weights and serum lipids of WT mice, but not TRPV1-/- mice, fed a high-fat diet. CONCLUSION: This study demonstrated that capsaicin activation of TRPV1-evoked increased Ca2+ influx in Cx43-mediated adipocyte-to-adipocyte communication promotes lipolysis in both vitro and vivo. TRPV1 activation by dietary capsaicin improves visceral fat remodeling through the up-regulation of Cx43.

Metformin-based treatment for obesity-related hypertension: a randomized, double-blind, placebo-controlled trial.

OBJECTIVES: Obesity and hypertension are associated with an adverse metabolic profile and systemic low-grade inflammation. Metformin reduces weight and inflammation in patients with diabetes, but it is unclear whether it has beneficial effects in patients without diabetes. The objective was to explore whether metformin-based treatment could benefit obesity-related hypertension without diabetes. METHODS: A randomized, double-blind, placebo-controlled factorial trial was conducted in 360 obese hypertensive patients without diabetes in Chongqing, China. After a 1-2-week run-in period, patients were randomly assigned to metformin (500 mg once per day) or placebo, as well as to an antihypertensive medication. Change in blood pressure, obesity measurements and metabolic profile were assessed at 24 weeks. RESULTS: The 180 participants randomized to metformin and 180 randomized to placebo were similar at baseline. At 24 weeks, metformin compared with placebo did not have significant effects on blood pressure, blood glucose, high-density or low-density lipoprotein cholesterol, but it did reduce total serum cholesterol (0.2 mmol/l, P = 0.038). Metformin also significantly reduced weight (-0.7 kg, P = 0.006), BMI (-0.2 kg/m, P = 0.024), waist circumference (-0.9 cm, P = 0.008), and both subcutaneous (-6.1 cm, P = 0.043) and visceral adiposity (-5.4 cm, P = 0.028) as measured by computed tomography, and lowered serum high-sensitivity C-reactive protein levels (-0.6 mg/dl, P < 0.001). There was no significant difference in adverse events (P = 0.785). CONCLUSIONS: Metformin has no effect on blood pressure and blood glucose levels, but it does reduce total cholesterol, abdominal obesity and C-reactive protein levels in obese hypertensive patients without diabetes.

[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. The MS risks of different types of abdominal obesity were compared. RESULTS: The prevalence rate of masked VFO of males was 10.9% (51/470), significantly higher than that of female (4.8%, 18/376). The prevalence rate of MS of the male patients with masked VFO was 43.1%, significantly higher than that of those in non-obesity group (25.0%), and lower than those of the males in the pseudo-VFO group (78.7%) and in the VFO group (88.6%), whereas the MS prevalence rate of the males in the pseudo-VFO group was significantly higher than those in the non-obesity and masked VFO groups. On the other hand, the MS prevalence rate of the female patients with masked VFO was 33.3%, not significantly different from that of the female patients in the non-obesity group (31.2%), but significantly lower than those of the pseudo-VFO and VFO groups (78.7% and 90.9% respectively). The MS prevalence rate of the female pseudo-VFO patients was also significantly higher than those in the non-obesity and masked VFO groups. Logistic regression analysis showed that WC and VA were independent risk factors for MS [OR (95% CI) = 1.13 (1.10-1.17), 1.01 (1.01-1.02), respectively, P < 0.01). CONCLUSION: Different types of abdominal obesity have important impacts on the risk of metabolic syndrome. Masked VFO, even though with normal WC, and pseudo-VFO have considerably higher cardiometabolic risks.