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.

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.

Effect of Bariatric Surgery on Metabolic Syndrome in Chinese Patients with Low Body Mass Index: a Propensity Score Matching Study.

BACKGROUND: Bariatric surgery (BS) is known to improve the components of metabolic syndrome (MS) in patients with obesity. However, few studies have evaluated the effect of BS on patients with MS at low BMI levels. The study aims to assess the effect of BS on MS in patients with low BMI by comparing BS with medical therapy (MT). METHODS: A total of 271 patients with MS who underwent BS and MT at a single institution were reviewed in this retrospective cohort study. A 1:1 propensity score matching was performed for the BS and MT groups with BMI<35 kg/m2. We analyzed the 5 years effect of BS versus MT on the remission of MS, its components, atherosclerotic cardiovascular disease (ASCVD) risk, and medication used. RESULTS: Patients in the MT group showed a decrease in the prevalence of MS to 62% at the 1st year and 10% at the 5th year. In the BS group, MS prevalence in patients with BMI<35 kg/m2 decreased to 30% and 9% at the 1st and 5th year, whereas in patients with BMI≥35 kg/m2 was 26% and 7%, respectively. The 10-year ASCVD risk and the lifetime ASCVD were significantly decreased 5 years after BS in patients with BMI<35 kg/m2. The number and daily drug dose of hypoglycemic drugs, antihypertensive medications, and lipid-lowering drugs were reduced from baseline in both BS and MT groups. CONCLUSION: Bariatric surgery significantly improves MS remission rates and long-term cardiovascular risk in Chinese patients with metabolic syndrome and a BMI <35 kg/m2.

Effect of bariatric surgery versus medical therapy on long-term cardiovascular risk in low BMI Chinese patients with type 2 diabetes: a propensity score-matched analysis.

BACKGROUND: Reducing the risk of death due to cardiovascular disease (CVD) is an important direction for diabetes prevention and treatment. The Chinese population with type 2 diabetes (T2D) has a high risk of developing CVD at relatively low body mass index (BMI) levels. Currently, no studies have evaluated the effect of bariatric surgery versus medical therapy on long-term CVD risk in patients with T2D and low BMI. OBJECTIVES: To compare bariatric surgery versus medical therapy for long-term CVD risk in Chinese patients with T2D and low BMI by using the China Prediction for ASCVD Risk equations and the United Kingdom Prospective Diabetes Study risk engine. SETTING: University hospital, China. METHODS: Medical records of patients with T2D with a BMI <35 kg/m2 undergoing bariatric surgery or medical therapy from May 2010 to December 2018 were reviewed. A 1:1 propensity score matching was performed by using 7 preoperative characteristics. Variables for calculating CVD risk scores over the 5-year follow-up were assessed. RESULTS: A total of 684 patients with T2D underwent bariatric surgery (n = 75) or medical therapy (n = 609), and 52 pairs of matched subjects were selected from both groups after propensity score matching. The 10-year and lifetime atherosclerotic CVD risk by using the China Prediction for ASCVD Risk equation at 5 years follow-up period in the bariatric surgery group improved significantly compared with the medical therapy group. In the fifth year of follow-up, the 10-year risk of coronary heart disease, fatal coronary heart disease, stroke, and fatal stroke by using the United Kingdom Prospective Diabetes Study risk engine were much lower in the bariatric surgery group than in the medical therapy group (10.37 ± 5.64% versus 27.25 ± 7.28%, P = .004; 6.3 ± 4.5% versus 22.3 ± 7.35%, P = .002; 4.97 ± 3.73% versus 15.05 ± 3.63%, P = .001; .59 ± .45% versus 1.52 ± .14%, P < .001. respectively). The use of glucose-lowering medications, including insulin, was reduced from baseline in both groups, and patients in the bariatric surgery group required significantly fewer of these medications than those in the medical therapy group. CONCLUSION: Bariatric surgery in patients with T2D and low BMI conferred a lower calculated risk of CVD compared with medical therapy over 5 years of follow-up.

Impact of metabolic surgery on 10-year cardiovascular disease risk in Chinese individuals with type 2 diabetes.

BACKGROUND: In recent years, many reports have highlighted that metabolic surgery may ameliorate the cardiovascular risk in morbidly obese patients with or without type 2 diabetes (T2D). However, few studies have evaluated the long-term cardiovascular disease (CVD) risk after metabolic surgery in T2D patients with a low body mass index (BMI). OBJECTIVES: To use the Prediction for ASCVD Risk in China (China-PAR) equations and United Kingdom Prospective Diabetes Study (UKPDS) risk engine to assess the 10-year CVD risk in low-BMI T2D patients after metabolic surgery. SETTING: University hospital, China. METHODS: We retrospectively reviewed our prospectively collected data of T2D patients who underwent metabolic surgery at our hospital between 2010 and 2018. We included patients who met the criteria for calculating a 10-year cardiovascular risk score by the China-PAR equations and UKPDS risk engine. Demographic characteristics, anthropometric variables, and glycolipid metabolic parameters were assessed preoperatively and during a 4-year follow-up period. Patients with a BMI < 30 kg/m2 were compared with those with a BMI > 30 kg/m2. RESULTS: We evaluated 117 patients, of whom 62 (53%) had a BMI < 30 kg/m2 and 55 (47%) had a BMI > 30 kg/m2. Patients with a BMI < 30 kg/m2 were significantly older and had a longer duration of diabetes. The rate of complete T2D remission in the group of patients with BMIs < 30 kg/m2 was significantly lower than that in the group with BMIs > 30 kg/m2 (35.2% versus 56.1%, respectively; P = .042). The overall 10-year and lifetime atherosclerotic cardiovascular disease risks were reduced from 4.2% to 2.3% and 25.3% to 13.9%, respectively (both P < .05), at 1 year postoperatively using the China-PAR equation. The overall 10-year coronary heart disease (CHD) and fatal CHD risks were reduced by 48.1% and 53.1%, respectively, at 1 year after surgery using the UKPDS risk engine. The advantages of metabolic surgery in reducing CVD risks are similar in both BMI groups, whether using the China-PAR equation or the UKPDS risk engine. CONCLUSION: The 10-year CVD risk in T2D patients with BMIs < 30 kg/m2 and BMIs > 30 kg/m2 were significantly reduced after metabolic surgery, although the rate of complete T2D remission T2Din patients with BMIs < 30 kg/m2 was lower than that in patients with BMIs > 30 kg/m2. The China-PAR equation is a reliable and useful clinical tool for CVD risk evaluation in Chinese patients after metabolic surgery.

Short versus long biliopancreatic limb in Roux-en-Y gastric bypass surgery for treatment of type 2 diabetes mellitus.

INTRODUCTION: Although laparoscopic Roux-en-Y gastric bypass (RYGB) is still widely accepted as a valid procedure in the treatment of obesity and type 2 diabetes mellitus (T2DM), there continues to be a significant controversy about how long the Roux and biliopancreatic limb should be bypassed for optimum results. AIM: To assess the effect of a longer biliopancreatic limb (BPL) length on glycemic control after RYGB in T2DM patients. MATERIAL AND METHODS: Eighty-four patients with uncontrolled T2DM who underwent RYGB between May 2010 and April 2017 were collected from the prospectively designed database. Forty patients (S-BPL group) received BPL lengths ≤ 50 cm, including 30 cm (n = 1), 40 cm (n = 1), and 50 cm (n = 38). Forty-four patients (L-BPL group) received 100 cm BPL. Anthropometry, serum glucose and lipid metabolic parameters were measured at baseline and 1, 3, 6, 12, 24 and 36 months after surgery. RESULTS: Comparing the two groups, there were no significant differences in anthropometric and biochemical measures, except the weight and body mass index, which were higher in the S-BPL group (85.91 ±20.32 vs. 76.25 ±16.99, p = 0.038; 31.87 ±6.61 vs. 28.7 ±4.29, p = 0.005) compared to the L-BPL group. The body weight, glucose and lipid metabolic parameters decreased over time and then remained essentially stable from the first year in both groups. Two years after surgery, the remission (HbA1c% ≤ 6%) of T2DM was 31.2% in the S-BPL group and 37.5% in the L-BPL group (p = 0.685). CONCLUSIONS: With consistent total small bowel bypass (AL + BPL) lengths, lengthening of the BPL from 30 to 100 cm did not affect the post-RYGB glycemic control and weight loss.

The Use of Visceral Adiposity Index to Predict Diabetes Remission in Low BMI Chinese Patients After Bariatric Surgery.

BACKGROUND: Visceral Adiposity Index (VAI) is considered to be a reliable indicator for evaluation of visceral adipose dysfunction and cardiovascular disease risk. However, no previous studies have reported the VAI variation after bariatric surgery and the predictive effect of preoperative VAI on diabetes remission. The aim of this study is to evaluate whether preoperative VAI is useful to predict diabetes remission in low BMI Chinese patients after bariatric surgery. METHODS: Eighty-seven type 2 diabetes mellitus patients with BMI < 35 kg/m2 underwent bariatric surgery from May 2010 to March 2018 in our hospital. VAI, glycolipid metabolic parameters, and anthropometric variables were measured before and 4 years after surgery. Complete remission was defined as follows: HbA1c < 6%, FPG < 5.6 mmol/L, achieved without anti-diabetic medication. Analysis included using binary logistic regression to identify predictors and ROC curves to determine clinically useful cutoff values. RESULTS: Seventy-four patients (85.1%) underwent Roux-en-Y gastric bypass (RYGB), while the remaining 13 patients (14.9%) underwent sleeve gastrectomy (SG). Patients' weight, glycemic control, and lipid profiles were improved significantly after surgery (p < 0.05). Complete remission of T2DM was found in 35 patients (40.2%) 1 year after surgery. VAI decreased from baseline 4.41 to 1.74 in 3 months after surgery (p < 0.05) and showed a downward trend over the period from 6 months to 4 years. Patients with complete remission had a significantly shorter duration of diabetes, lower HbA1c level, and higher VAI, in comparison to those without remission. Binary logistics regression and ROC curves analysis confirm that VAI, HbA1c, and duration of diabetes can predict diabetes remission after bariatric surgery, and the VAI of 4.46 is a useful threshold for predicting surgical efficacy. CONCLUSION: VAI is a significant predictor of diabetes remission for lower BMI patients with T2DM following bariatric surgery in China. The VAI of 4.46 is a useful threshold for predicting surgical efficacy. Multi-center and larger prospective studies are needed to confirm our findings.

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.

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.

Non-insulin determinant pathways maintain glucose homeostasis upon metabolic surgery.

Insulin is critical for glucose homeostasis, and insulin deficiency or resistance leads to the development of diabetes. Recent evidence suggests that diabetes can be remitted independent of insulin. However, the underlying mechanism remains largely elusive. In this study, we utilized metabolic surgery as a tool to identify the non-insulin determinant mechanism. Here, we report that the most common metabolic surgery, Roux-en-Y gastric bypass (RYGB), reduced insulin production but persistently maintained euglycemia in healthy Sprague-Dawley (SD) rats and C57 mice. This reduction in insulin production was associated with RYGB-mediated inhibition of pancreatic preproinsulin and polypyrimidine tract-binding protein 1. In addition, RYGB also weakened insulin sensitivity that was evaluated by hyperinsulinemic-euglycemic clamp test and downregulated signaling pathways in insulin-sensitive tissues. The mechanistic evidence suggests that RYGB predominately shifted the metabolic profile from glucose utilization to fatty acid oxidation, enhanced the energy expenditure and activated multiple metabolic pathways through reducing gut energy uptake. Importantly, the unique effect of RYGB was extended to rats with islet disruption and patients with type 2 diabetes. These results demonstrate that compulsory rearrangement of the gastrointestinal tract can initiate non-insulin determinant pathways to maintain glucose homeostasis. Based on the principle of RYGB action, the development of a noninvasive intervention of the gastrointestinal tract is a promising therapeutic route to combat disorders characterized by energy metabolism dysregulation.

Effects of Laparoscopic Roux-en-Y Gastric Bypass for Type 2 Diabetes Mellitus: Comparison of BMI > 30 and < 30 kg/m2.

BACKGROUND: Recently, many studies focused on type 2 diabetes mellitus (T2DM) patients with body mass index (BMI) < 30 kg/m2 and suggested that those patients might benefit from Roux-en-Y gastric bypass (RYGB). However, evidence on its effectiveness to improve T2DM patients with BMI < 30 kg/m2 is still lacking. The aim of this study is to explore whether T2DM patients with BMI < 30 kg/m2 get similar surgical effect from RYGB compared with those patients with BMI > 30 kg/m2. METHODOLOGY: Seventy patients with uncontrolled T2DM underwent laparoscopic RYGB from May 2010 to December 2015 in the GI Department of Daping Hospital. Weight, BMI, waist circumference, glucose, and lipid metabolic parameters were collected and evaluated at baseline and 1, 3, 6, 12, and 24 months postsurgery. Patients with BMI < 30 kg/m2 were compared with those with BMI > 30 kg/m2. RESULTS: Among the 70 patients, 47 (67.1%) BMI < 30 kg/m2, and 23 (32.9%) BMI > 30 kg/m2. Patients with BMI < 30 kg/m2 are significantly older; they are female predominant and have longer duration of diabetes. The complete remission of T2DM was 28.2% of the BMI < 30 kg/m2 group and 57.9% of the BMI > 30 kg/m2 group (p = 0.029). There was no significant difference in the change of glucose and lipid metabolic parameters of both groups. FPG, 2hPG, and HbA1c% levels were significantly improved after 1 month (p < 0.05), and then remained essentially stable from the sixth month in both groups. CONCLUSIONS: The 2-year study has shown that RYGB is a safe and effective procedure in treating T2DM with BMI < 30 kg/m2, although the complete remission of T2DM in the BMI < 30 kg/m2 group is lower than the BMI > 30 kg/m2 group.

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.

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.

Ameliorating Endothelial Mitochondrial Dysfunction Restores Coronary Function via Transient Receptor Potential Vanilloid 1-Mediated Protein Kinase A/Uncoupling Protein 2 Pathway.

Coronary heart disease arising from atherosclerosis is a leading cause of cardiogenic death worldwide. Mitochondria are the principal source of reactive oxygen species (ROS), and defective oxidative phosphorylation by the mitochondrial respiratory chain contributes to ROS generation. Uncoupling protein 2 (UCP2), an adaptive antioxidant defense factor, protects against mitochondrial ROS-induced endothelial dysfunction in atherosclerosis. The activation of transient receptor potential vanilloid 1 (TRPV1) attenuates vascular dysfunction. Therefore, whether TRPV1 activation antagonizes coronary lesions by alleviating endothelial mitochondrial dysfunction and enhancing the activity of the protein kinase A/UCP2 pathway warrants examination. ApoE(-/-), ApoE(-/-)/TRPV1(-/-), and ApoE(-/-)/UCP2(-/-) mice were fed standard chow, a high-fat diet (HFD), or the HFD plus 0.01% capsaicin. HFD intake profoundly impaired coronary vasodilatation and myocardial perfusion and shortened the survival duration of ApoE(-/-) mice. TRPV1 or UCP2 deficiency exacerbated HFD-induced coronary dysfunction and was associated with increased ROS generation and reduced nitric oxide production in the endothelium. The activation of TRPV1 by capsaicin upregulated UCP2 expression via protein kinase A phosphorylation, thereby alleviating endothelial mitochondrial dysfunction and inhibiting mitochondrial ROS generation. In vivo, dietary capsaicin supplementation enhanced coronary relaxation and prolonged the survival duration of HFD-fed ApoE(-/-) mice. These effects were not observed in ApoE(-/-) mice lacking the TRPV1 or UCP2 gene. The upregulation of protein kinase A /UCP2 via TRPV1 activation ameliorates coronary dysfunction and prolongs the lifespan of atherosclerotic mice by ameliorating endothelial mitochondrial dysfunction. Dietary capsaicin supplementation may represent a promising intervention for the primary prevention of coronary heart disease.