Associations between Life's Essential 8 and post-stroke depression and all-cause mortality among US adults.

BACKGROUND: Depression is the common mental disease after stroke. Our objective was to investigate the correlation of Life's Essential 8 (LE8), the recently updated evaluation of cardiovascular health, with the occurrence of post-stroke depression (PSD) and all-cause mortality among United States (US) adults. METHODS: Participants with stroke were chosen from the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2018. The relationship between LE8 and the risk of PSD was assessed through weighted multiple logistic models. A restricted cubic spline was employed for the examination of correlations. To demonstrate the stability of the results, sensitivity analysis and subgroup analysis were carried out. Furthermore, Cox regression models were used for the correlation between LE8 and all-cause mortality. RESULTS: In this study, a total of 1071 participants were included for analysis. It was observed that LE8 score and PSD risk shared an inverse relationship in per 10 points increase [OR = 0.62 (0.52-0.74, P < 0.001)] in logistic regression models. The analysis of restricted cubic spline demonstrated approximately a noticeable inverse linear association between LE8 score and PSD risk. Sensitivity analysis verified the stability of the findings. Moreover, no statistically significant interactions were identified in subgroup analysis. A reverse association between LE8 score and all-cause mortality was also observed with a 10-point increase [HR = 0.85 (0.78-0.94, P < 0.001)] in cox regression models. CONCLUSIONS: A negative correlation was discovered between LE8 score and PSD and all-cause mortality risk among US adults. We need to conduct large-scale prospective studies to further validate our results.

Association between composite dietary antioxidant index and coronary heart disease among US adults: a cross-sectional analysis.

BACKGROUND: The Composite Dietary Antioxidant Index (CDAI) is a dietary antioxidant score that plays a protective role in many diseases, including depression, osteoporosis, papillomavirus infection, etc. However, the association between CDAI and coronary heart disease (CHD) is currently unclear. We aim to explore the correlations between CDAI and the risk of CHD. METHODS: Eligible participants were obtained from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. All participants in this cross-sectional study are required to undergo two separate 24-h dietary recall interviews. Average daily intakes of dietary antioxidants were used to calculate CDAI. CHD status was determined through a questionnaire. Weighted multiple logistic regression models were used to evaluate the relationship between CDAI and CHD. Moreover, we also used restricted cubic spline to explore Non-linear correlations. Sensitivity analysis using unweighted logistic analysis and subgroup analysis were used to demonstrate the stability of the results. RESULTS: A total of 34,699 participants were eligible for analysis.Compared to the participants without CHD, the participants with CHD showed lower levels of CDAI. After adjusting confounding factors in the multivariate weighted logistic regression model, CDAI was inversely associated with CHD (Q4 vs. Q1, OR = 0.65 (0.51-0.82, P < 0.001). Restricted cubic spline showed that there was a negative non-linear correlation (L-shaped) between CDAI and CHD, suggesting a potential saturation effect at higher CDAI levels, with the inflection point of 0.16. Sensitivity analysis showed that the results were stable. No significant statistically interaction was showed in subgroup analysis. CONCLUSIONS: There was a negative non-linear correlation between CDAI and CHD in US adults. However, further prospective studies are still needed to reveal their relationship.

Melatonin Attenuates Mitochondrial Damage in Aristolochic Acid-Induced Acute Kidney Injury.

Aristolochic acid (AA), extracted from Aristolochiaceae plants, plays an essential role in traditional herbal medicines and is used for different diseases. However, AA has been found to be nephrotoxic and is known to cause aristolochic acid nephropathy (AAN). AA-induced acute kidney injury (AKI) is a syndrome in AAN with a high morbidity that manifests mitochondrial damage as a key part of its pathological progression. Melatonin primarily serves as a mitochondria-targeted antioxidant. However, its mitochondrial protective role in AA-induced AKI is barely reported. In this study, mice were administrated 2.5 mg/kg AA to induce AKI. Melatonin reduced the increase in Upro and Scr and attenuated the necrosis and atrophy of renal proximal tubules in mice exposed to AA. Melatonin suppressed ROS generation, MDA levels and iNOS expression and increased SOD activities in vivo and in vitro. Intriguingly, the in vivo study revealed that melatonin decreased mitochondrial fragmentation in renal proximal tubular cells and increased ATP levels in kidney tissues in response to AA. In vitro, melatonin restored the mitochondrial membrane potential (MMP) in NRK-52E and HK-2 cells and led to an elevation in ATP levels. Confocal immunofluorescence data showed that puncta containing Mito-tracker and GFP-LC3A/B were reduced, thereby impeding the mitophagy of tubular epithelial cells. Furthermore, melatonin decreased LC3A/B-II expression and increased p62 expression. The apoptosis of tubular epithelial cells induced by AA was decreased. Therefore, our findings revealed that melatonin could prevent AA-induced AKI by attenuating mitochondrial damage, which may provide a potential therapeutic method for renal AA toxicity.

Neohesperidin Protects Angiotensin II-Induced Hypertension and Vascular Remodeling.

Vascular remodeling due to hypertension is one of the major health challenges facing countries around the world. Neohesperidin, a flavonoid glycoside found in citrus fruits, is an antioxidant. Neohesperidin has been studied for a variety of diseases in addition to hypertension. In this study, angiotensin II was used to induce hypertension in mice (490 ng/kg/min, 14 days). We used H&E, Masson, immunofluorescence, dihydroethidine and qPCR to evaluate the effect of Nehesperidin (50 mg/kg/day, 16 days) on pathological hypertension in mice. Estimating the effect of Nehesperidin on human umbilical vein endothelial cells and vascular smooth muscle cells stimulated by angiotensin II. We found that neohesperidin inhibited angiotensin II-induced hypertension in mice. Neohesperidin reduced angiotensin II-induced vascular hypertrophy, fibrosis, inflammation and oxidative stress in vivo. Neohesperidin inhibited angiotensin II-induced ROS and DNA damage in human umbilical vein endothelial cells. Neohesperidin inhibited angiotensin II-induced migration of vascular smooth muscle cells. The results showed that Nehesperidin acts as an antioxidant and could significantly inhibit angiotensin II induced hypertension and vascular remodeling in vitro and in vivo.

Roles of NOD1/Rip2 signal pathway in carotid artery remodelling in spontaneous hypertensive rats.

Nucleotide-binding and oligomerization domain (NOD) receptor is a member of inherent immunity recognition receptor family. We investigated the NOD1/Rip2 signalling pathway on carotid arterial remodelling in spontaneously hypertensive rats (SHRs). SHRs were treated with NOD1 agonist (iE-DAP), inhibitor (ML130), or normal saline. We determined the NOD1 and Rip2 expression in carotid artery tissues, serum tumour necrosis factor-α (TNF-α) and monocyte chemotactic protein-1 (MCP-1). The carotid artery remodelling in 16-week SHRs was higher than that of 8-week SHRs and 16-week Wistar-Kyoto (WKY) rats. Expression of NOD1, Rip2, MCP-1 and TNF-α in 16-week SHRs was higher than that of 8-week SHRs and 16-week WKY rats. Blood pressure in iE-DAP-treated SHRs was higher than SHR-C group (no treatment), together with MCP-1, TNF-α, NOD1 and Rip2 expression, as well as carotid artery remodelling. In ML130-treated group, these aspects were completely the opposite. Taken together, inhibition of NOD1/Rip2 signalling pathway could delay the vascular remodelling process.

A case of primary aldosteronism with a negative aldosterone-to-renin ratio.

BACKGROUND: Primary aldosteronism (PA), as a cause of secondary hypertension, can cause more serious cardiovascular damage than essential hypertension. The aldosterone-to-renin ratio (ARR) is recommended as the most reliable screening method for PA, but ARR screening is often influenced by many factors. PA cannot be easily excluded when negative ARR. CASE PRESENTATION: We report the case of a 45-year-old Chinese man with resistant hypertension. Three years ago, he underwent a comprehensive screening for secondary hypertension, including the ARR, and the result was negative. After that, the patient's blood pressure was still poorly controlled with four kinds of antihypertensive drugs, the target organ damage of hypertension progressed, and hypokalaemia was difficult to correct. When the patient was hospitalized again for comprehensive examination, we found that aldosterone levels had significantly increased, although the ARR was negative. An inhibitory test with saline was further carried out, and the results suggested that aldosterone was not inhibited; therefore, PA was diagnosed. We performed a unilateral adenoma resection for this patient, and spironolactone was continued to control blood pressure. After the operation, blood pressure is well controlled, and hypokalaemia is corrected. CONCLUSION: When the ARR is negative, PA cannot be easily excluded. Comprehensive analysis and diagnosis should be based on the medication and clinical conditions of patients.

Assessment of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker on the split renal function in the patients with primary hypertension.

ABSTRACT: Bilateral kidney damage in hypertensive patients is not parallel. Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB), as a commonly used antihypertensive drug, could protect kidney function and delay its deterioration. Most studies focused on overall renal function, but the researches on split renal function (SRF) are rare. We investigated the effects of ACEI/ARB on the SRF in patients with primary hypertension.Patients with primary hypertension (n = 429; male: 213; female: 216) admitted to our department between January 2014 and December 2016 were included in this study. The glomerular filtration rate (GFR) of split and total renal function were determined using diethylenetriaminepentaacetic acid tagged with 99mTc renal dynamic imaging method. For the same patient, the side with high GFR was considered as higher GFR kidney, whereas that with a low GFR was considered as lower GFR kidney. The split function score (Q value) was utilized to evaluate the differences of bilateral renal function. The patients were divided into 3 groups based on the Q values (Group 1, Q value <5%; Group 2, Q value of 5%-10%; Group 3, Q value ≥10%). All the patients received antihypertensive therapy based on ACEI/ARB. The renal dynamic imaging was performed in the 1-year follow-up to investigate the changes of the SRF.Compared with the baseline level, significant decline was noticed in the serum creatinine (Scr) in Group 2 and Group 3 (P < .05). The cystatin C in Group 3 showed significant decline (P < .05). Compared with the baseline, there was significant decline in the Q value in Group 2, whereas the GFR of lower GFR kidney showed significant increase (P < .05). No statistical differences were noticed in the Q value and split GFR in Group 1 and Group 3 (P > .05).In primary hypertension patients, ACEI/ARB therapy could improve the SRF of lower GFR kidney in the presence of certain differences between the SRF. As a result, the SRF difference was reduced. In case of Q value in a range of 5% to 10%, ACEI/ARB could improve the renal function effectively. It may be significant for the design of antihypertensive drugs.

Effects of irbesartan on phenotypic alterations in monocytes and the inflammatory status of hypertensive patients with left ventricular hypertrophy.

BACKGROUND: Circulating monocytes and tissue macrophages play complex roles in the pathogenesis of hypertension and the resulting target organ damage. In this study, we observed alterations in the monocyte phenotype and inflammatory state of hypertensive patients with left ventricular hypertrophy (LVH) and studied the effects of irbesartan in these patients. This study might reveal a novel mechanism by which irbesartan alleviates LVH, and it could provide new targets for the prevention and treatment of hypertensive target organ damage. METHODS: CD163 and CD206 expression on monocytes and IL-10 and TNF-α levels in the serum of hypertensive patients with or without LVH and of healthy volunteers were detected. Furthermore, we treated monocytes from the LVH group with different concentrations of irbesartan, and then, CD163, CD206, IL-10 and TNF-α expression was detected. RESULTS: We found, for the first time, that the expression of CD163, CD206 and IL-10 in the LVH group was lower than that in the non-LVH group and healthy control group, but the TNF-α level in the LVH group was significantly higher. Irbesartan upregulated the expression of CD163 and CD206 in hypertensive patients with LVH in a concentration-dependent manner. Irbesartan also increased the expression of IL-10 and inhibited the expression of TNF-α in monocyte culture supernatants in a concentration-dependent manner. CONCLUSIONS: Our data suggest that inflammation was activated in hypertensive patients with LVH and that the monocyte phenotype was mainly proinflammatory. The expression of proinflammatory factors increased while the expression of anti-inflammatory factors decreased. Irbesartan could alter the monocyte phenotype and inflammatory status in hypertensive patients with LVH. This previously unknown mechanism may explain how irbesartan alleviates LVH. Trail registration The study protocols were approved by the Ethical Committee of the Second Affiliated Hospital of Dalian Medical University. Each patient signed the informed consent form.

The Role of the NOD1/Rip2 Signaling Pathway in Myocardial Remodeling in Spontaneously Hypertensive Rats.

BACKGROUND Chronic hypertension changes the function and structure of the heart and blood vessels. This study aimed to explore the role of the NOD1/Rip2 (nucleotide-binding oligomerization domain 1/receptor-interacting protein 2) signaling pathway in myocardial remodeling in spontaneously hypertensive rats (SHRs). MATERIAL AND METHODS Blood pressure was measured using a tail cuff. The cardiac structure was observed using echocardiography. Slices of the myocardium were stained with hematoxylin and eosin. The expression of NOD1 and Rip2 was detected using real-time polymerase chain reaction, western blot, and immunohistochemistry. The content and distribution of collagen in the myocardium were observed using Van Gieson staining. Enzyme-linked immunosorbent assay was used to detect the interleukin-1 (IL-1) concentrations. SHRs were treated with the NOD1 agonist iE-DAP and NOD1 inhibitor ML130. RESULTS The NOD1 agonist increased blood pressure in SHRs, and the NOD1 inhibitor decreased blood pressure; the interventricular septum thickness (IVST) and left ventricular posterior wall thickness (LVPWT) of the agonist-treated group were thicker than those of the control group, and the antagonist exerted the opposite effects. The levels of the NOD1 and Rip2 mRNAs and proteins, serum IL-1 concentration, and myocardial collagen volume fraction (CVF%) increased in SHRs in the NOD1 agonist group, but the levels of NOD1 and Rip2, serum IL-1 concentration, and myocardial collagen volume fraction (CVF%) decreased in SHRs in the NOD1 inhibitor group. CONCLUSIONS NOD1/Rip2 expression increased during the progression of myocardial remodeling in SHRs. The NOD1 agonist increased NOD1 expression and promoted myocardial remodeling, while the NOD1 antagonist reduced NOD1/Rip2 expression and protected against myocardial remodeling.

Neohesperidin inhibits cardiac remodeling induced by Ang II in vivo and in vitro.

Cardiac hypertrophy and remodeling are among the major health challenges facing countries around the world today. Neohesperidin plays an important role in influencing cell apoptosis, cell growth, tumorigenesis and tumor microenvironment, but the mechanism and role of Neohesperidin in cardiac hypertrophy and remodeling caused by Angiotensin II has not been fully elucidated. This study used Angiotensin II to induce cardiac hypertrophy and cardiac remodeling in mice. Echocardiography was used to evaluate cardiac function, H&E and Masson trichrome staining were used to detect myocardial histological changes. Cardiac cell size was determined by WGA staining. The protein content of the signaling pathway was detected by Western blot, and the mRNA expression of fibrosis and hypertrophy markers was detected by qPCR. DHE staining was used to detect oxidative stress. We also observed the effect of Neohesperidin on Ang II-induced NRCMs. The results showed that neohesperidin can significantly inhibit Ang II-induced myocardial contractile dysfunction, cardiac hypertrophy, myocardial fibrosis, myocardial oxidative stress and inflammation. These results suggest that Neohesperidin can alleviate cardiac hypertrophy and remodeling caused by Ang II, and its mechanism may be related to the inhibition of multiple signaling pathways.

Analysis of critical negative rake angle and friction characteristics in orthogonal cutting of AL1060 and T2.

The stagnant region often appears in front of the tool cutting edge, which is caused by mechanical inlay and excessive pressing in plastic metal cutting with large negative rake angle tools at a low speed. It results in the change of the effective negative rake angle which can affect the flow characteristics of material, the quality of machined surface and the abrasion loss of cutting tools. However, the critical negative rake angle model based on the existence of the stagnant region has not been reported yet. Therefore, in order to investigate the critical negative rake angle value considering the stagnant region, a critical negative rake angle model based on the principle of minimum required energy is established, and the correctness of the theoretical model is verified by orthogonal cutting experiments. At the same time, the influence of the critical value of the large negative rake angle tool on the machined surface quality is studied through different cutting experiments. These experimental results show that the deviations of both experimental and theoretical critical negative rake angle are less than 5% during the orthogonally cutting of the aluminium (AL1060) and copper (T2) materials by the negative rake angle tool. Meanwhile, the critical negative rake angle is related to the adhesive friction coefficient of tool-workpiece contact surface. The analysis of friction characteristics shows that the deviation values of both theoretical and experimental critical negative rake angle are proportional to the coefficient of adhesive friction and the thickness of the stagnant region. Critical negative rake angle has a significant effect on roughness and residual stress of the machined surface.

Aqp-1 Gene Knockout Attenuates Hypoxic Pulmonary Hypertension of Mice.

Objective- Hypoxic pulmonary hypertension (HPH) is characterized by proliferative vascular remodeling. Abnormal pulmonary artery smooth muscle cells proliferation and endothelial dysfunction are the primary cellular bases of vascular remodeling. AQP1 (aquaporin-1) is regulated by oxygen level and has been observed to play a role in the proliferation and migration of pulmonary artery smooth muscle cells. The role of AQP1 in HPH pathogenesis has not been directly determined to date. To determine the possible roles of AQP1 in the pathogenesis of HPH and explore its possible mechanisms. Approach and Results- Aqp1 knockout mice were used, and HPH model was established in this study. Primary pulmonary artery smooth muscle cells, primary mouse lung endothelial cells, and lung tissue sections from HPH model were used. Immunohistochemistry, immunofluorescence and Western blot, cell cycle, apoptosis, and migration analysis were performed in this study. AQP1 expression was upregulated by chronic hypoxia exposure, both in pulmonary artery endothelia and medial smooth muscle layer of mice. Aqp1 deficiency attenuated the elevation of right ventricular systolic pressures and mitigated pulmonary vascular structure remodeling. AQP1 deletion reduced abnormal cell proliferation in pulmonary artery and accompanied with accumulation of HIF (hypoxia-inducible factor). In vitro, Aqp1 deletion reduced hypoxia-induced proliferation, apoptosis resistance, and migration ability of primary cultured pulmonary artery smooth muscle cells and repressed HIF-1α protein stability. Furthermore, Aqp1 deficiency protected lung endothelial cells from apoptosis in response to hypoxic injury. Conclusions- Our data showed that Aqp1 deficiency could attenuate hypoxia-induced vascular remodeling in the development of HPH. AQP1 may be a potential target for pulmonary hypertension treatment.

Alterations of the Gut Microbiome in Hypertension.

Introduction: Human gut microbiota is believed to be directly or indirectly involved in cardiovascular diseases and hypertension. However, the identification and functional status of the hypertension-related gut microbe(s) have not yet been surveyed in a comprehensive manner. Methods: Here we characterized the gut microbiome in hypertension status by comparing fecal samples of 60 patients with primary hypertension and 60 gender-, age-, and body weight-matched healthy controls based on whole-metagenome shotgun sequencing. Results: Hypertension implicated a remarkable gut dysbiosis with significant reduction in within-sample diversity and shift in microbial composition. Metagenome-wide association study (MGWAS) revealed 53,953 microbial genes that differ in distribution between the patients and healthy controls (false discovery rate, 0.05) and can be grouped into 68 clusters representing bacterial species. Opportunistic pathogenic taxa, such as, Klebsiella spp., Streptococcus spp., and Parabacteroides merdae were frequently distributed in hypertensive gut microbiome, whereas the short-chain fatty acid producer, such as, Roseburia spp. and Faecalibacterium prausnitzii, were higher in controls. The number of hypertension-associated species also showed stronger correlation to the severity of disease. Functionally, the hypertensive gut microbiome exhibited higher membrane transport, lipopolysaccharide biosynthesis and steroid degradation, while in controls the metabolism of amino acid, cofactors and vitamins was found to be higher. We further provided the microbial markers for disease discrimination and achieved an area under the receiver operator characteristic curve (AUC) of 0.78, demonstrating the potential of gut microbiota in prediction of hypertension. Conclusion: These findings represent specific alterations in microbial diversity, genes, species and functions of the hypertensive gut microbiome. Further studies on the causality relationship between hypertension and gut microbiota will offer new prospects for treating and preventing the hypertension and its associated diseases.

Grape seed procyanidin extract attenuates hypoxic pulmonary hypertension by inhibiting oxidative stress and pulmonary arterial smooth muscle cells proliferation.

Hypoxia-induced oxidative stress and excessive proliferation of pulmonary artery smooth muscle cells (PASMCs) play important roles in the pathological process of hypoxic pulmonary hypertension (HPH). Grape seed procyanidin extract (GSPE) possesses antioxidant properties and has beneficial effects on the cardiovascular system. However, the effect of GSPE on HPH remains unclear. In this study, adult Sprague-Dawley rats were exposed to intermittent chronic hypoxia for 4 weeks to mimic a severe HPH condition. Hemodynamic and pulmonary pathomorphology data showed that chronic hypoxia significantly increased right ventricular systolic pressures (RVSP), weight of the right ventricle/left ventricle plus septum (RV/LV+S) ratio and median width of pulmonary arteries. GSPE attenuated the elevation of RVSP, RV/LV+S, and reduced the pulmonary vascular structure remodeling. GSPE also increased the levels of SOD and reduced the levels of MDA in hypoxia-induced HPH model. In addition, GSPE suppressed Nox4 mRNA levels, ROS production and PASMCs proliferation. Meanwhile, increased expression of phospho-STAT3, cyclin D1, cyclin D3 and Ki67 in PASMCs caused by hypoxia was down-regulated by GSPE. These results suggested that GSPE might potentially prevent HPH via antioxidant and antiproliferative mechanisms.

NOD2 agonist promotes the production of inflammatory cytokines in VSMC in synergy with TLR2 and TLR4 agonists.

OBJECTIVE: To investigate the expression of NOD2 in human VSMCs, its role in the production of inflammatory cytokines in VSMC and the possible interaction of NOD2-mediated signaling pathway with those mediated by TLR2 and TLR4. METHODS: Human coronary artery smooth muscle cells were stimulated with NOD2 agonist MDP alone or in combination with either TLR2 agonist PAM3 or TLR4 agonist LPSs. The mRNA expression of NOD2 and FGF-2 were measured by RT-PCR. The concentration of IL-8 and TNF-α in the culture supernatants was determined by ELISA. VSMC proliferation ability was analyzed by MTT assay. RESULTS: MDP up regulated the expression of NOD2 mRNA in VSMC in a time-dependent manner, up regulated the expression of FGF-2 mRNA in VSMC, induced the production of IL-8 and TNF-α, and promoted the proliferation of VSMC. Additionally, MDP synergied with LPS and PAM3 to promote the proliferation of VSMC and induce the production of IL-8 and TNF-α. CONCLUSION: The activation of NOD2-mediated innate immune signaling pathway can increase the proliferation ability of VSMC and induce the production of inflammatory cytokines in VSMC. It is also shown a synergistic effect with TLR2- and TLR4-mediated signaling pathways in this process.

The relation between left ventricular geometric patterns and left ventricular midwall mechanics in hypertensive patients.

To evaluate the alteration of myocardial contractility in hypertensive patients with different left ventricular geometric patterns by the end-systolic stress-midwall fractional shortening relation. Echocardiography was applied to study the left ventricular geometry and cardiac function among 117 cases of essential hypertension, with 45 normal cases as control(s). Left ventricular mass index (LVMI) and relative wall thickness (RWT) were calculated using echocardiographic data. All patients were divided into four kinds of left ventricular geometry pattern based on LVMI and RWT. Patients of the eccentric hypertrophy group suffered the most serious damage of left ventricular systolic function. Myocardial contractility shown by end-systolic stress-midwall fractional shortening relation was significantly decreased in the concentric remodeling group, eccentric hypertrophy group and concentric hypertrophy group, and those with concentric hypertrophy showed the worst contractility. The degree of myocardial contractility damage was different in patients with different left ventricular geometric patterns. Geometric changes may have compensated for the reduction of myocardial contractility in some phases in order to maintain the normal pump function.