Gsα Regulates Macrophage Foam Cell Formation During Atherosclerosis.

BACKGROUND: Many cardiovascular pathologies are induced by signaling through G-protein-coupled receptors via Gsα (G protein stimulatory α subunit) proteins. However, the specific cellular mechanisms that are driven by Gsα and contribute to the development of atherosclerosis remain unclear. METHODS: High-throughput screening involving data from single-cell and bulk sequencing were used to explore the expression of Gsα in atherosclerosis. The differentially expression and activity of Gsα were analyzed by immunofluorescence and cAMP measurements. Macrophage-specific Gsα knockout (Mac-GsαKO) mice were generated to study the effect on atherosclerosis. The role of Gsα was determined by transplanting bone marrow and performing assays for foam cell formation, Dil-ox-LDL (oxidized low-density lipoprotein) uptake, chromatin immunoprecipitation, and luciferase reporter assays. RESULTS: ScRNA-seq showed elevated Gnas in atherosclerotic mouse aorta's cholesterol metabolism macrophage cluster, while bulk sequencing confirmed increased GNAS expression in human plaque macrophage content. A significant upregulation of Gsα and active Gsα occurred in macrophages from human and mouse plaques. Ox-LDL could translocate Gsα from macrophage lipid rafts in short-term and promote Gnas transcription through ERK1/2 activation and C/EBPß phosphorylation via oxidative stress in long-term. Atherosclerotic lesions from Mac-GsαKO mice displayed decreased lipid deposition compared with those from control mice. Additionally, Gsα deficiency alleviated lipid uptake and foam cell formation. Mechanistically, Gsα increased the levels of cAMP and transcriptional activity of the cAMP response element binding protein, which resulted in increased expression of CD36 and SR-A1. In the translational experiments, inhibiting Gsα activation with suramin or cpGN13 reduced lipid uptake, foam cell formation, and the progression of atherosclerotic plaques in mice in vivo. CONCLUSIONS: Gsα activation is enhanced during atherosclerotic progression and increases lipid uptake and foam cell formation. The genetic or chemical inactivation of Gsα inhibit the development of atherosclerosis in mice, suggesting that drugs targeting Gsα may be useful in the treatment of atherosclerosis.

Influence of baseline arterial stiffness on effects of intensive compared with standard blood pressure control: a post hoc analysis of the STEP trial.

BACKGROUND: The benefits and risks of intensive versus standard systolic blood pressure (SBP) treatment in older patients with arterial stiffness (AS) remains unclear. This study aims to investigate the interaction between the baseline AS and SBP treatments on cardiovascular outcomes. METHODS: In this post hoc analysis of the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial, we involved 6865 participants with complete data regarding baseline brachial-ankle pulse wave velocity (baPWV). Patients were categorized by baseline AS status (AS, baPWV ≥ 1800 cm/s; non-AS, baPWV < 1800 cm/s). The primary outcome was a composite of cardiovascular events. The secondary outcomes were stroke, acute coronary syndrome (ACS), major cardiovascular events (MACE), and all-cause death. Cox regression was used to calculate hazard ratios for the outcomes. RESULTS: During a mean follow-up of 2.69 years, a total of 248 primary outcome events and 81 all-cause deaths occurred. The hazard ratios for the primary outcome were 0.76 (95% confidence interval (CI), 0.54-1.09) and 0.63 (95% CI, 0.43-0.92) in the AS and non-AS groups, respectively (P for interaction = 0.43), and that for stroke was 0.58 (95% CI, 0.33-1.02) and 0.48 (95% CI, 0.23-0.99) in the AS and non-AS groups, respectively (P for interaction = 0.68). Effects of intensive SBP treatment on safety outcomes and all-cause death were also similar in the two groups (P for interaction > 0.05 for all). CONCLUSIONS: In the STEP trial, the beneficial effects of intensive SBP treatment were similar among those in the AS group and the non-AS group at baseline. TRIAL REGISTRATION: STEP ClinicalTrials.gov number, NCT03015311. Registered 2 January 2017.

Intestinal Flora Modulates Blood Pressure by Regulating the Synthesis of Intestinal-Derived Corticosterone in High Salt-Induced Hypertension.

RATIONALE: High-salt diet is one of the most important risk factors for hypertension. Intestinal flora has been reported to be associated with high salt-induced hypertension (hSIH). However, the detailed roles of intestinal flora in hSIH pathogenesis have not yet been fully elucidated. OBJECTIVE: To reveal the roles and mechanisms of intestinal flora in hSIH development. METHODS AND RESULTS: The abovementioned issues were investigated using various techniques including 16S rRNA gene sequencing, untargeted metabolomics, selective bacterial culture, and fecal microbiota transplantation. We found that high-salt diet induced hypertension in Wistar rats. The fecal microbiota of healthy rats could dramatically lower blood pressure (BP) of hypertensive rats, whereas the fecal microbiota of hSIH rats had opposite effects. The composition, metabolism, and interrelationship of intestinal flora in hSIH rats were considerably reshaped, including the increased corticosterone level and reduced Bacteroides and arachidonic acid levels, which tightly correlated with BP. The serum corticosterone level was also significantly increased in rats with hSIH. Furthermore, the above abnormalities were confirmed in patients with hypertension. The intestinal Bacteroides fragilis could inhibit the production of intestinal-derived corticosterone induced by high-salt diet through its metabolite arachidonic acid. CONCLUSIONS: hSIH could be transferred by fecal microbiota transplantation, indicating the pivotal roles of intestinal flora in hSIH development. High-salt diet reduced the levels of B fragilis and arachidonic acid in the intestine, which increased intestinal-derived corticosterone production and corticosterone levels in serum and intestine, thereby promoting BP elevation. This study revealed a novel mechanism different from inflammation/immunity by which intestinal flora regulated BP, namely intestinal flora could modulate BP by affecting steroid hormone levels. These findings enriched the understanding of the function of intestinal flora and its effects on hypertension.

Sirtuin 3 deficiency aggravates angiotensin II-induced hypertensive cardiac injury by the impairment of lymphangiogenesis.

Lymphangiogenesis is possibly capable of attenuating hypertension-induced cardiac injury. Sirtuin 3 (SIRT3) is an effective mitochondrial deacetylase that has the potential to modulate this process; however, its role in hypertension-induced cardiac lymphangiogenesis to date has not been investigated. Our experiments were performed on 8-week-old wild-type (WT), SIRT3 knockout (SIRT3-KO) and SIRT3 overexpression (SIRT3-LV) mice infused with angiotensin II (Ang II) (1000 ng/kg per minute) or saline for 28 days. After Ang II infusion, SIRT3-KO mice developed a more severe cardiac remodelling, less lymphatic capillaries and lower expression of lymphatic marker when compared to wild-type mice. In comparison, SIRT3-LV restored lymphangiogenesis and attenuated cardiac injury. Furthermore, lymphatic endothelial cells (LECs) exposed to Ang II in vitro exhibited decreased migration and proliferation. Silencing SIRT3 induced functional decrease in LECs, while SIRT3 overexpression LECs facilitated. Moreover, SIRT3 may up-regulate lymphangiogenesis by affecting vascular endothelial growth factor receptor 3 (VEGFR3) and ERK pathway. These findings suggest that SIRT3 could promote lymphangiogenesis and attenuate hypertensive cardiac injury.

SIRT3 Ablation Deteriorates Obesity-Related Cardiac Remodeling by Modulating ROS-NF-κB-MCP-1 Signaling Pathway.

Obesity and the associated complications are a major public health issue as obesity incidence increases yearly, worldwide. Effects of obesity on heart failure have been reported previously. Obesity-related cardiac remodeling includes structural and functional dysfunctions, in which cardiac inflammation and fibrosis play a key role. The main mitochondrial deacetylase, SIRT3 participates in numerous cellular processes; however, its role in obesity-related cardiac remodeling remains unclear. In our study, high-fat diet (HFD) feeding induced downregulation of SIRT3 protein level in mice. SIRT3-KO mice fed on HFD exhibited higher cardiac dysfunction and cardiac remodeling compared with the wild-type controls. Further study revealed increases in collagen accumulation and inflammatory cytokine expression including MCP-1, IL-6, TGF-ß, TNF-α in mice fed on HFD compared with chow diet, with higher levels observed in SIRT3-KO mice. Furthermore, significantly high levels of cardiac MCP-1 expression and macrophage infiltration, and ROS generation and activated NF-κB were observed in HFD-fed SIRT3-KO mice. We presumed that SIRT3 ablation-mediated MCP-1 upregulation is attributed to ROS-NF-κB activation. Thus, we concluded that SIRT3 prevents obesity-related cardiac remodeling by attenuating cardiac inflammation and fibrosis, through modulation of ROS-NF-κB-MCP-1 pathway.

Sirt3 promotes sensitivity to sunitinib-induced cardiotoxicity via inhibition of GTSP1/JNK/autophagy pathway in vivo and in vitro.

Sunitinib malate is a multi-targeted tyrosine kinase inhibitor used extensively for treatment of human tumors. However, cardiovascular adverse effects of sunitinib limit its clinical use. It is pivotal to elucidate molecular targets that mediate sunitinib-induced cardiotoxicity. Sirtuin 3 (Sirt3) is an effective mitochondrial deacetylase that has been reported to regulate sensitivity of different types of cells to chemotherapies, but roles of Sirt3 in sunitinib-induced cardiotoxicity have not been investigated. In the present study, we established wild type, Sirt3-knockout, and Sirt3-overexpressing mouse models of sunitinib (40 mg kg-1 day-1 for 28 days)-induced cardiotoxicity and examined cardiovascular functions and pathological changes. We further cultured wild type, Sirt3-knockout, and Sirt3-overexpressing primary mouse cardiac pericytes and analyzed sunitinib (10 µMol for 48 h)-induced alterations in cellular viability, cell death processes, and molecular pathways. Our results show that sunitinib predominantly induced hypertension, left ventricular systolic dysfunction, and cardiac pericyte death accompanied with upregulation of Sirt3 in cardiac pericytes, and these cardiotoxicities were significantly attenuated in Sirt3-knockout mice, but aggravated in Sirt3-overexpressing mice. Mechanistically, sunitinib induced cardiac pericyte death through inhibition of GSTP1/JNK/autophagy pathway and Sirt3 interacted with and inhibited GSTP1, further inhibiting the pathway and aggravating sunitinib-induced pericyte death. Conclusively, we demonstrate that Sirt3 promotes sensitivity to sunitinib-induced cardiotoxicity via GSTP1/JNK/autophagy pathway. Our results suggest Sirt3 might be a potential target for developing cardioprotective therapies for sunitinib-receiving patients.

The Expression and Clinical Significance of Spleen Tyrosine Kinase in Patients with Coronary Heart Disease.

BACKGROUND Our research was designed to investigate the relationship of spleen tyrosine kinase (Syk) and inflammatory factors with coronary heart disease (CHD) and the risk factors of CHD. MATERIAL AND METHODS In our study, 226 patients were enrolled, from October 2017 to March 2018. Clinical and biochemical data were collected. We collected samples of peripheral blood monocytes (PBMs) from the enrolled patients. The patients were divided in 4 groups: patients without coronary artery disease (control group), patients with stable angina pectoris (SAP group), patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS group), and patients with ST-segment elevation acute myocardial infarction group (STEMI group). We detect the protein levels of Syk and inflammatory factors expression by western blot. RESULTS Our results found the protein levels of Syk and inflammatory factors expression in the NSTE-ACS and STEMI groups were higher than those in the SAP and control groups. The protein levels of Syk and inflammatory factors expression in the SAP group were higher than those in the control group. Moreover, there were many risk factors significantly associated with Syk. Besides that, these risk factors were also independent risk factors of CHD. CONCLUSIONS Our results found that the level of Syk was associated with the severity of CHD. From our study, we found that higher levels of Syk and inflammatory factors protein were associated with worse results of the CHD. For the first time, Syk was reported to be a promising therapeutic factor for CHD patients.

Trimetazidine ameliorates sunitinib-induced cardiotoxicity in mice via the AMPK/mTOR/autophagy pathway.

Context: Sunitinib (SU) is a multi-targeted tyrosine kinase inhibitor anticancer agent whose clinical use is often limited by cardiovascular complications. Trimetazidine (TMZ) is an anti-angina agent that has been demonstrated cardioprotective effects in numerous cardiovascular conditions, but its potential effects in SU-induced cardiotoxicity have not been investigated. Objective: This study investigates the effect of TMZ in sunitinib-induced cardiotoxicity in vivo and in vitro and molecular mechanisms. Materials and methods: Male 129S1/SvImJ mice were treated with vehicle, SU (40 mg/kg/d) or SU and TMZ (20 mg/kg/d) via oral gavage for 28 days, and cardiovascular functions and cardiac protein expressions were examined. H9c2 cardiomyocytes were treated with vehicle, SU (2-10 µM) or SU and TMZ (40-120 µM) for 48 h, and cell viability, apoptosis, autophagy, and protein expression was tested. Results: SU induces hypertension (systolic blood pressure [SBP] + 28.33 ± 5.00 mmHg) and left ventricular dysfunction (left ventricular ejection fraction [LVEF] - 11.16 ± 2.53%) in mice. In H9c2 cardiomyocytes, SU reduces cell viability (IC50 4.07 µM) and inhibits the AMPK/mTOR/autophagy pathway (p < 0.05). TMZ co-administration with SU reverses SU-induced cardiotoxicity in mice (SBP - 23.75 ± 4.69 mmHg, LVEF + 10.95 ± 3.317%), alleviates cell viability loss in H9c2 cardiomyocytes (p < 0.01) and activates the AMPK/mTOR/autophagy pathway in vivo (p < 0.001) and in vitro (p < 0.05). Discussion and conclusions: Our results suggest TMZ as a potential cardioprotective approach for cardiovascular complications during SU regimen, and potentially for cardiotoxicity of other anticancer chemotherapies associated with cardiomyocyte autophagic pathways.

Recombinant leptin attenuates abdominal aortic aneurysm formation in angiotensin II-infused apolipoprotein E-deficient mice.

Vascular disease can manifest as stenotic plaques or ectatic aneurysms. Human abdominal aortic aneurysms (AAA) comprise an inflammatory disease characterized by the predominance of T helper type 2 (Th2) cytokine expression. Leptin has been clearly demonstrated to play an important role in regulating Th0 cell to Th1. So, we hypothesize that leptin has a protective effect on aneurysm formation. In this study, we demonstrated that intraperitoneal injection of leptin attenuated Ang II-induced AAA formation in ApoE-/- mice with no effect on serum lipids and systolic blood pressure. To investigate the mechanisms involved, we found that leptin pretreatment exhibited decreased protein expression of matrix metalloproteinase 2 (MMP-2) and MMP-9 and increased transforming growth factor-ß1 (TGF-ß1). We also examined potential mechanism of leptin as a modulator of the immune response. Our results proved that pretreatment with leptin downregulated protein expression of Th2 cytokine IL-4 and mRNA levels of GATA-3, the key transcription factor for Th2 polarization, and upregulated Th1 cytokine INF-γ and T-bet, the key transcription factor for Th1 polarization. Taken together, leptin, with the effect of regulation of Th1/Th2 cytokines, may have therapeutic potential for the treatment of AAA. Leptin may constitute a novel therapeutic strategy to prevent AAA formation.

Sirtuin 3 deficiency aggravates contrast-induced acute kidney injury.

BACKGROUND: Sirtuin 3 (Sirt3) is a key regulator of energy metabolism and oxidative stress. To investigate the role of Sirt3 in contrast-induced acute kidney injury (CIAKI), we established the model both in vivo and in vitro to explore the potential mechanisms. METHODS: In vivo, we established CIAKI models in wild-type (WT) and Sirt3-knockout (Sirt3-KO) mice. Blood urea nitrogen (BUN) and serum creatinine (Scr) were detected by enzyme-linked immunosorbent assay, Glomerular Filtration Rate (GFR) and creatinine clearance were also investigated. We detected the production of reactive oxygen species (ROS) via 2'7'-dichlorodihydro-fluorescein diacetate. The expressions of Sirt3, oxidative stress and apoptosis related markers (MnSOD, Catalase, Acetyl-MnSOD K68, Nox4, Bax, Bcl-2 and Caspase3) were measured and analyzed. In addition, we observed the effect of nicotinamide riboside (NR) on CIAKI in WT and Sirt3-KO mice. In vitro, Sirt3 was knocked out by siRNA transfection method in HK-2 cells. Sirt3, ROS, oxidative stress and apoptosis markers in HK-2 cells were also measured. RESULTS: Our data demonstrated that the levels of Scr and BUN in Sirt3-KO mice were increased while the levels of the GFR and creatinine clearance were decreased in CIAKI mice. In Sirt3-KO or siRNA groups, the activities of MnSOD and Catalase were markedly down-regulated. Also, the expression of Caspase3 were markedly increased and the ratio of Bcl-2/Bax was decreased, while the ROS level was increased in Sirt3 deficiency groups. NR ameliorated CIAKI in WT mice but not in Sirt3-KO mice. CONCLUSION: Our results suggest that Sirt3 deficiency aggravates contrast-induced acute kidney injury. Sirt3 is critical in NR-mediated renoprotection in CIAKI.

Melatonin attenuates angiotensin II-induced cardiomyocyte hypertrophy through the CyPA/CD147 signaling pathway.

Melatonin is well known for its cardioprotective effects; however, whether melatonin exerts therapeutic effects on cardiomyocyte hypertrophy remains to be investigated, as do the mechanisms underlying these effects, if they exist. Cyclophilin A (CyPA) and its corresponding receptor, CD147, which exists in a variety of cells, play crucial roles in modulating reactive oxygen species (ROS) production. In this study, we explored the role of the CyPA/CD147 signaling pathway in angiotensin II (Ang II)-induced cardiomyocyte hypertrophy and the protective effects exerted by melatonin against Ang II-induced injury in cultured H9C2 cells. Cyclosporine A, a specific CyPA/CD147 signaling pathway inhibitor, was used to manipulate CyPA/CD147 activity. H9C2 cells were then subjected to Ang II or CyPA treatment in either the absence or presence of melatonin. Our results indicate that Ang II induces cardiomyocyte hypertrophy through the CyPA/CD147 signaling pathway and promotes ROS production, which can be blocked by melatonin pretreatment in a concentration-dependent manner, in cultured H9C2 cells and that CyPA/CD147 signaling pathway inhibition protects against Ang II-induced cardiomyocyte hypertrophy. The protective effects of melatonin against Ang II-induced cardiomyocyte hypertrophy depend at least partially on CyPA/CD147 inhibition.

The histone demethylase PHF8 represses cardiac hypertrophy upon pressure overload.

BACKGROUND: Mammalian hearts undergo hypertrophy upon pressure overload to support increased workload. Sustained hypertrophy results in cardiac decompensation and subsequently heart failure. The mechanism that prevents the development of cardiac hypertrophy is still not fully understood. Here we elucidate the anti-hypertrophic role of the histone demethylase PHF8. METHODS AND RESULTS: PHF8 protein and mRNA levels were down-regulated in human failing hearts, mouse hypertrophic hearts and neonatal rat ventricle myocytes that underwent hypertrophy. Then we generated a cardiac-specific PHF8 transgenic mice, and found that PHF8 overexpression reversed cardiac dysfunction, hypertrophy and fibrosis upon pressure overload. In vivo evidence showed that PHF8 blocked protein synthesis and hypertrophic fetal genes expression. Furthermore, we found that PHF8 inhibited Akt-mTOR pathway in hypertrophic hearts and neonatal rat ventricle myocytes, and rapamycin treatment rescues the effects of PHF8 loss. CONCLUSION: These results indicate that PHF8 serves as an endogenous factor that the host uses to attenuate cardiac hypertrophy upon cardiac overload. Strategies based on its enhancement might be of benefit in the treatment of hypertrophic cardiomyopathy.

Activation of SIRT3 by resveratrol ameliorates cardiac fibrosis and improves cardiac function via the TGF-ß/Smad3 pathway.

Sirtuins [sirtuin (SIRT)1-SIRT7] mediate the longevity-promoting effects of calorie restriction in yeast, worms, flies, and mice. Additionally, SIRT3 is the only SIRT analog whose increased expression has been shown to be associated with longevity in humans. The polyphenol resveratrol (RSV) is the first compound discovered able to mimic calorie restriction by stimulating SIRTs. In the present study, we report that RSV activated SIRT3 in cardiac fibroblasts both in vivo and in vitro. Moreover, in wild-type mice, RSV prevented cardiac hypertrophy in response to hypertrophic stimuli. However, this protective effect was not observed in SIRT3 knockout mice. Additionally, the activation of SIRT3 by RSV ameliorated collagen deposition and improved cardiac function. In isolated cardiac fibroblasts, pretreatment with RSV suppressed fibroblast-to-myoblast transformation by inhibiting the transforming growth factor-ß/Smad3 pathway. Therefore, these data indicate that the activation of SIRT3 by RSV could ameliorate cardiac fibrosis and improve cardiac function via the transforming growth factor-ß/Smad3 pathway.

Role of SIRT3 in Angiotensin II-induced human umbilical vein endothelial cells dysfunction.

BACKGROUND: SIRT3, a member of the sirtuin family of NAD(+)-dependent deacetylases, resides primarily in the mitochondria and has been shown to deacetylate several metabolic and respiratory enzymes that regulate important mitochondrial functions. Previous researches show an important role of SIRT3 in regulating the production of reactive oxygen species (ROS), and highlight the ability of SIRT3 to protect cells from oxidative damage. A key substance of renin-angiotensin-aldosterone system (RAAS), Angiotensin II (AngII) can induce cells dysfunction by increasing the production of ROS. In this paper, we focus on the role of SIRT3 in AngII-induced human umbilical vein endothelial cells (HUVECs) dysfunction. METHODS: To study the influence of AngII on SIRT3 expression, HUVECs were treated with AngII of 10(-7), 10(-6), 10(-5) mol/L for 24 h. SIRT3 expression was detected by wester-blotting analysis and RT-PCR. In addition, to research the role of SIRT3 in AngII-induced HUVECs,we used SIRT3 siRNA to knock down SIRT3 expression in HUVECs. Cells pretreated with negative control siRNA or SIRT3 siRNA were exposed to AngII for 24 h, and endothelial nitric oxide synthase (eNOS) expression, eNOS activity, total level of nitric oxide (NO) and ROS generation of each group were detected. RESULTS: Here we show that AngII treatment could increase generation of ROS, and decrease eNOS activity and total level of NO, while upregulated eNOS expression as a compensatory mechanism. The stimulation of AngII upregulated the expression of SIRT3 in HUVECs. SIRT3 siRNA worsen the AngII-induced effects above, besides, downregulated eNOS protein expression. CONCLUSION: These data suggest that SIRT3 plays a role of protection in AngII-induced HUVECs dysfunction via regulation of ROS generation.

Amiodarone-induced epididymitis: a pathologically confirmed case report and review of the literature.

We report a case of amiodarone-induced epididymitis and review the pertinent literature. This disease is currently a diagnosis of exclusion and is believed to be self-limiting. We found new evidence for the pathological diagnosis and identified amiodarone-like crystals in the epididymis as a pathological mechanism of this disease. This case also suggests that amiodarone-induced epididymitis is not self-limiting. Continued use of amiodarone according to the current guidelines led to a bilateral epididymectomy. We recommend withdrawal or reduction of amiodarone dosage immediately once the signs and symptoms of epididymitis present in this population of patients. When epididymitis does not seem to be caused by an infection or any other identifiable etiology, this should not be overlooked by the cardiologist, urologist or general practitioner. These findings and recommendations should help reduce the suffering of patients and improve their clinical outcomes.

SIRT3 regulates cardiolipin biosynthesis in pressure overload-induced cardiac remodeling by PPARγ-mediated mechanism.

Cardiac remodeling is the primary pathological feature of chronic heart failure (HF). Exploring the characteristics of cardiac remodeling in the very early stages of HF and identifying targets for intervention are essential for discovering novel mechanisms and therapeutic strategies. Silent mating type information regulation 2 homolog 3 (SIRT3), as a major mitochondrial nicotinamide adenine dinucleotide (NAD)-dependent deacetylase, is required for mitochondrial metabolism. However, whether SIRT3 plays a role in cardiac remodeling by regulating the biosynthesis of mitochondrial cardiolipin (CL) is unknown. In this study, we induced pressure overload in wild-type (WT) and SIRT3 knockout (SIRT3-/-) mice via transverse aortic constriction (TAC). Compared with WT mouse hearts, the hearts of SIRT3-/- mice exhibited more-pronounced cardiac remodeling and fibrosis, greater reactive oxygen species (ROS) production, decreased mitochondrial-membrane potential (ΔΨm), and abnormal mitochondrial morphology after TAC. Furthermore, SIRT3 deletion aggravated TAC-induced decrease in total CL content, which might be associated with the downregulation of the CL synthesis related enzymes cardiolipin synthase 1 (CRLS1) and phospholipid-lysophospholipid transacylase (TAFAZZIN). In our in vitro experiments, SIRT3 overexpression prevented angiotensin II (AngII)- induced aberrant mitochondrial function, CL biosynthesis disorder, and peroxisome proliferator-activated receptor gamma (PPARγ) downregulation in cardiomyocytes; meanwhile, SIRT3 knockdown exacerbated these effects. Moreover, the addition of GW9662, a PPARγ antagonist, partially counteracted the beneficial effects of SIRT3 overexpression. In conclusion, SIRT3 regulated PPARγ-mediated CL biosynthesis, maintained the structure and function of mitochondria, and thereby protected the myocardium against cardiac remodeling.

Management of nocturnal hypertension: An expert consensus document from Chinese Hypertension League.

Nocturnal hypertension is highly prevalent among Chinese and Asian populations, which is mainly attributed to high salt intake and high salt sensitivity. Nocturnal hypertension increases the risk of cardiovascular and all-cause mortality, independent of daytime blood pressure (BP). However, it can usually be detected by 24-h ambulatory BP monitoring, rather than routine office or home BP measurement, thus is often underdiagnosed in clinical practice. Currently, no specific guidance is available for the management of nocturnal hypertension in China or worldwide. Experts from the Chinese Hypertension League summarized the epidemiologic and pathophysiologic characteristics and clinical phenotype of nocturnal hypertension and provided consensus recommendations on optimal management of nocturnal hypertension, with the goal of maximally reducing the cardiovascular disease risks. In this consensus document, 24-h ABPM is recommended for screening and diagnosis of nocturnal hypertension, especially in the elderly, patients with diabetes, chronic kidney diseases, obstructive sleep apnea and other conditions prone to high nocturnal BP. Lifestyle modifications including salt intake restriction, exercise, weight loss, sleep improvement, and mental stress relief are recommended. Long-acting antihypertensive medications are preferred for nocturnal and 24-h BP control. Some newly developed agents, renal denervation, and other device-based therapy on nocturnal BP reduction are evaluated.

Efficacy and safety of olmesartan medoxomil-amlodipine besylate tablet in Chinese patients with essential hypertension: A prospective, single-arm, multi-center, real-world study.

There lacks real-world study with a large sample size assessing olmesartan medoxomil-amlodipine besylate (OM-AML) tablet. Therefore, this study aimed to evaluate the efficacy and safety of OM-AML tablet in patients with essential hypertension. Totally, 1341 patients from 36 medical centers with essential hypertension who took OM-AML (20/5 mg) tablet were analyzed in the current prospective, single-arm, multi-center, real-world study (SVK study). Seated systolic blood pressure (SeSBP) and seated diastolic blood pressure (SeDBP) at baseline, week (W)4 and W8 were measured. The mean (±SE) change of SeSBP/SeDBP was -10.8 ± 0.4/-6.6 ± 0.3 mmHg at W4 and -12.7 ± 0.5/-7.6 ± 0.3 mmHg at W8, respectively. At W4, 78.8% and 29.0% patients achieved BP target by China and American Heart Association (AHA) criteria; at W8, 84.7% and 36.5% patients reached blood pressure (BP) target by China and AHA criteria, accordingly. Meanwhile, 80.2% and 86.4% patients achieved BP response at W4 and W8, respectively. Home-measured SeSBP and SeDBP decreased from W1 to W8 (both p < .001). Besides, patients' and physicians' satisfaction were elevated at W8 compared with W0 (both p < .001). The medication possession rate was 94.8% from baseline to W4 and 91.3% from baseline to W8. The most common drug-related adverse events were nervous system disorders (4.6%), vascular disorders (2.6%), and general disorders and administration site conditions (2.3%) by system organ class, which were generally mild and manageable. In conclusion, OM-AML tablet is one of the best antihypertensive agents in patients with essential hypertension.

Efficacy and safety of olmesartan medoxomil­amlodipine besylate tablets (Sevikar®) in older patients with essential hypertension: Subgroup analysis from the Sevikar study.

Essential hypertension is a notable threat for the older (age, ≥65 years) population. However, to the best of our knowledge, a real-world study assessing olmesartan medoxomil-amlodipine besylate (OM-AML) tablets in older Chinese patients with essential hypertension has not been performed. Therefore, the present study aimed to evaluate the efficacy and safety of OM-AML tablets in these patients. A total of 463 older Chinese patients with essential hypertension treated with OM-AML (20/5 mg) tablets (Sevikar®) were analyzed in a prospective, single-arm, multi-center, real-world study. Seated systolic blood pressure (SeSBP) and seated diastolic blood pressure (SeDBP) at baseline, and at week (W)4 and W8 after OM-AML tablet administration were measured. The mean ± standard error change of SeSBP/SeDBP was -10.3±0.8/-4.6±0.5 and -12.5±0.8/-5.6±0.5 mmHg at W4 and W8, respectively. At W4, 74.1 and 26.8% of patients achieved BP target according to the China and American Heart Association (AHA) criteria, while at W8, 78.0 and 38.7% of patients reached these BP targets accordingly. Finally, 76.5 and 80.5% of patients achieved BP response at W4 and W8, respectively. Furthermore, home-measured SeSBP and SeDBP were significantly decreased from W1 to W8 (both P<0.001). Additionally, the satisfaction of both patients and physicians was elevated at W8 compared with at W0 (both P<0.001). The medication possession rate from baseline to W4 and W8 was 95.5 and 92.5%. The most common drug-associated adverse events by system organ classes were nervous system disorder (4.5%), vascular disorder (2.8%), and general disorder and administration site conditions (2.6%), which were generally mild. In conclusion, OM-AML tablets may be considered effective and safe in lowering BP, enabling the achievement of guideline-recommended BP targets in older Chinese patients with essential hypertension.