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.

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.

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.

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.

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.

Fibulin7 Mediated Pathological Cardiac Remodeling through EGFR Binding and EGFR-Dependent FAK/AKT Signaling Activation.

Adverse remodeling after myocardial infarction (MI) result in heart failure and sudden cardiac death. Fibulin7 (FBLN7) is an adhesion protein excreted into the extracellular matrix that functions in multiple biological processes. However, whether and how FBLN7 affects post-MI cardiac remodeling remains unclear. Here, the authors identify FBLN7 as a critical profibrotic regulator of adverse cardiac remodeling. They observe significantly upregulated serum FBLN7 levels in MI patients with left ventricular remodeling compared to those without MI. Microarray dataset analysis reveal FBLN7 is upregulated in human heart samples from patients with dilated and hypertrophic cardiomyopathy compared with non-failing hearts. The authors demonstrate that FBLN7 deletion attenuated post-MI cardiac remodeling, leading to better cardiac function and reduced myocardial fibrosis, whereas overexpression of FBLN7 results in the opposite effects. Mechanistically, FBLN7 binds to the epidermal growth factor receptor (EGFR) through its EGF-like domain, together with the EGF-like calcium-binding domain, and induces EGFR autophosphorylation at tyrosine (Y) 1068 and Y1173, which activates downstream focal adhesion kinase/AKT signaling, thereby leading to fibroblast-to-myofibroblast transdifferentiation. In addition, FBLN7-EGFR mediates this signal transduction, and the fibrotic response is effectively suppressed by the inhibition of EGFR activity. Taken together, FBLN7 plays an important role in cardiac remodeling and fibrosis after MI.

Visit-to-Visit Blood Pressure Variability and Cardiovascular Outcomes in Patients Receiving Intensive Versus Standard Blood Pressure Control: Insights From the STEP Trial.

BACKGROUND: The clinical prognostic value of visit-to-visit blood pressure (BP) variability (BPV) is debatable, and relative studies among patients receiving BP control to achieve lower BP targets are limited. METHODS: We analyzed a dataset from the STEP trail (Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients) to investigate the relationship between visit-to-visit BPV and cardiovascular events in patients with hypertensive aged 60 to 80 years. Visit-to-visit BPV was defined as the coefficient of variation, SD, delta, average real variability, and variability independent of the mean of BP measured at 6-, 9-, 12-, 15-, and 18-month follow-up visits. We computed hazard ratios for the risks associated with a 1-SD increase in BPV indexes in multivariable cox regression models. RESULTS: Among 7678 patients from the STEP trial, after adjustment for multiple confounders, diastolic BPV indexes were significantly associated with the primary composite end point (hazard ratios ≥1.21; P≤0.029) in the standard group, while there was no association between the clinical outcomes and systolic BPV (P≥0.091). In the intensive treatment group, either systolic or diastolic BPV was no association with clinical outcomes(P≥0.30). Sensitivity analyses using an alternative method to calculate BPV based on 7 BP records generated confirmatory results. CONCLUSIONS: In older adults with hypertension, visit-to-visit diastolic BPV is an independent predictor of adverse health outcomes in the standard treatment group. However, BPV did not have prognostic value in the intensive treatment group. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03015311.

Effects of resveratrol supplementation on cardiac remodeling in hypertensive patients: a randomized controlled clinical trial.

Resveratrol (RES) has been demonstrated to be protective in the cardiovascular system in animal studies, but the evidence is limited in humans. The purpose of the study was to evaluate the effect of RES supplementation on cardiac remodeling in patients with hypertension. Eighty Subjects were randomly divided into RES group (plus RES 400 mg/d in addition to conventional therapy, n = 43) and control group (conventional therapy, n = 37). The main outcomes of the study were changes within cardiac-remodeling parameters. Secondary outcomes were changes in anthropometric parameters, arterial stiffness parameters and mechanism indices. There was no statistically significant difference between the RES group and control group in terms of baseline characteristics. After 6 months, the RES group had smaller left atrial, lower E/e', higher left ventricular global longitudinal strain and lower biomarkers indicating cardiac fibrosis (expressed by decreases in procollagen type I C-peptide and galectin-3) compared to the control group. However, there was no significant difference in left ventricular structure between the two groups. Although the RES group showed a significant decrease in brachial-ankle pulse wave velocity compared to the pre-intervention value, the difference between the RES and the control groups was not obvious. What's more, compared with the control group, the serum levels of sirtuin3, superoxide dismutase and klotho were significantly increased in the RES group. In conclusion, RES supplementation can alleviate left atrial remodeling, improve left ventricular diastolic function and may alleviate cardiac fibrosis in hypertensive patients, and could be used as an adjunct to conventional therapies of hypertensive heart disease.

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.

Correction: Mouse Sirt3 promotes autophagy in AngII-induced myocardial hypertrophy through the deacetylation of FoxO1.

[This corrects the article DOI: 10.18632/oncotarget.13429.].

SS31 Alleviates Pressure Overload-Induced Heart Failure Caused by Sirt3-Mediated Mitochondrial Fusion.

Heart failure caused by pressure overload is one of the leading causes of heart failure worldwide, but its pathological origin remains poorly understood. It remains critical to discover and find new improvements and treatments for pressure overload-induced heart failure. According to previous studies, mitochondrial dysfunction and myocardial interstitial fibrosis are important mechanisms for the development of heart failure. The oligopeptide Szeto-Schiller Compound 31 (SS31) can specifically interact with the inner mitochondrial membrane and affect the integrity of the inner mitochondrial membrane. Whether SS31 alleviates pressure overload-induced heart failure through the regulation of mitochondrial fusion has not yet been confirmed. We established a pressure-overloaded heart failure mouse model through TAC surgery and found that SS31 can significantly improve cardiac function, reduce myocardial interstitial fibrosis, and increase the expression of optic atrophy-associated protein 1 (OPA1), a key protein in mitochondrial fusion. Interestingly, the role of SS31 in improving heart failure and reducing fibrosis is inseparable from the presence of sirtuin3 (Sirt3). We found that in Sirt3KO mice and fibroblasts, the effects of SS31 on improving heart failure and improving fibroblast transdifferentiation were disappeared. Likewise, Sirt3 has direct interactions with proteins critical for mitochondrial fission and fusion. We found that SS31 failed to increase OPA1 expression in both Sirt3KO mice and fibroblasts. Thus, SS31 can alleviate pressure overload-induced heart failure through Sirt3-mediated mitochondrial fusion. This study provides new directions and drug options for the clinical treatment of heart failure caused by pressure overload.

Chinese Classical Music Lowers Blood Pressure and Improves Left Ventricular Hypertrophy in Spontaneously Hypertensive Rats.

High blood pressure (BP) plays an important role in the pathogenesis and development of cardiovascular diseases and multi-organ damages. Music has been well known to elicit emotional changes, such as anxiolytic effects. However, whether music therapy lowers BP in spontaneously hypertensive rats (SHR) and the potential mechanism remains unknown. SHRs were, respectively exposed to white noise (WN), Western classical music (WM), Chinese classical music (CCM), rock music (RM), and bisoprolol treatment. WN and WM did not lower systemic BP, but CCM and RM significantly lowered BPs in SHRs. The effects of CCM therapy on lowering systemic BPs is comparable to that of bisoprolol at the dose of low to medium. Combination of CCM treatment with bisoprolol further improved systemic BPs and myocardial hypertrophy in SHRs, compared to CCM treatment or bisoprolol alone. Furthermore, IHC and WB analysis indicated that CCM therapy inhibited the ß1/cAMP/PKA and α1/PLC/PKC signalings, but didn't alter the ß2/PI3K/Akt signaling. Above all, CCM therapy lowers systemic BPs and alleviates myocardial hypertrophy in hypertensive rats, which may be caused by the inhibitions of ß1/cAMP/PKA and α1/PLC/PKC signalings.

Tongxinluo May Alleviate Inflammation and Improve the Stability of Atherosclerotic Plaques by Changing the Intestinal Flora.

Intestinal flora plays an important role in atherosclerosis. Tongxinluo, as a multi-target Chinese medicine to improve atherosclerosis, whether it can improve atherosclerosis by affecting the intestinal flora is worth exploring. We established a vulnerable plaque model of atherosclerosis in New Zealand white rabbits by high cholesterol diet and balloon injury (HCB), and performed Tongxinluo intervention. We detected the level of inflammation by immunohistochemistry, Western Blot, and ELISA, analyzed plaque characteristics by calculating the vulnerability index, and analyzed the changes of gut microbiota and metabolites by 16S rRNA gene sequencing and untargeted metabolomic sequencing. The results showed that Tongxinluo intervention improved plaque stability, reduced inflammatory response, inhibited NLRP3 inflammatory pathway, increased the relative abundance of beneficial bacteria such as Alistipes which reduced by HCB, and increased the content of beneficial metabolites such as trans-ferulic acid in feces. Through correlation analysis, we found that some metabolites were significantly correlated with some bacteria and some inflammatory factors. In particular, the metabolite trans-ferulic acid was also significantly positively correlated with plaque stability. Our further studies showed that trans-ferulic acid could also inhibit the NLRP3 inflammatory pathway. In conclusion, Tongxinluo can improve plaque stability and reduce inflammation in atherosclerotic rabbits, which may be achieved by modulating intestinal flora and intestinal metabolism. Our study provides new views for the role of Tongxinluo in improving atherosclerotic vulnerable plaque, which has important clinical significance.

Value of the Systemic Immune-Inflammatory Index (SII) in Predicting the Prognosis of Patients With Peripartum Cardiomyopathy.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is a potentially life-threatening complication of pregnancy. The identification of early prognostic markers in patients diagnosed with PPCM is very important. The systemic immune-inflammation index (SII) is a new inflammatory biomarker, and the aim of this study was to evaluate the prognostic value of SII in patients with PPCM. METHODS: A total of 61 patients with PPCM who were admitted in our hospital from 2015 to 2020 were retrospectively analyzed in this study. The follow-up period of all patients was at least 6 months after diagnosis. Recovery of left ventricular (LV) systolic function was defined as the presence of left ventricular ejection fraction > 45%. The second endpoint was defined as composite adverse cardiac events, including cardiac death or hospitalization due to worsening heart failure. Univariate and multivariate logistic regression analysis were used to determine the independent predictors of non-recovery of LV systolic function. The receiver operating characteristic (ROC) curve analysis was used to establish a cut-off level of SII value to predict persistent LV systolic dysfunction. RESULTS: The follow-up duration was 40.5 ± 16.3 months. Among the 61 patients, 43 patients showed left ventricular recovery and 18 patients did not at the last follow-up visit. The baseline SII levels were significantly higher in the non-recovery group (P < 0.05). Multivariate logistic regression showed that the SII and left ventricular end-diastolic dimension (LVEDD) were independent predictors of persistent LV systolic dysfunction (OR: 1.177, 95% CI: 1.038-1.335, P = 0.011 and OR: 1.148, 95% CI: 1.011-1.304, P = 0.033, respectively). A SII value of 876 was the best cut-off value (the area under the curve was 0.791, 95% CI: 0.667-0.915, P < 0.05), and the sensitivity and specificity were 73 and 71%, respectively. CONCLUSIONS: The SII and LVEDD are independent prognostic factors for persistent LV systolic dysfunction in patients with PPCM. The SII may be a useful tool for identifying high-risk PPCM patients.

Effect of fecal microbiota transplantation on primary hypertension and the underlying mechanism of gut microbiome restoration: protocol of a randomized, blinded, placebo-controlled study.

BACKGROUND: Hypertension is currently the leading modifiable cause of global morbidity and mortality, leading to substantial health and financial burdens. Although multiple studies of management models and innovative therapeutic strategies for hypertension have been conducted, there are still gaps in the field, with a poor control rate reflecting a lack of novel, effective, clinically translated medication or intervention options. Recent animal and human studies repeatedly confirmed a link between the microbiota and hypertension. Of note is our previous study establishing a cause-and-effect relationship between the gut microbiota and blood pressure elevation. A hypothesis of gut microbiota intervention for treating hypertension is thus postulated, and fecal microbiota transplantation (FMT) from healthy donors was performed. METHODS: A multicenter, randomized, placebo-controlled, blinded clinical trial will be performed in 120 grade 1 hypertensive patients for 3 months. All recruited patients will be randomly assigned in a 1:1 ratio to take oral FMT capsules or placebo capsules on day 1, day 7, and day 14 and will be followed up on day 30, day 60, and day 90. The primary outcome is the change in office systolic blood pressure from baseline to day 30. The main secondary outcomes are BP indicators, including changes in systolic and diastolic blood pressure from office and 24-h ambulatory blood pressure monitoring; assessments of ankle-branchial index and pulse wave velocity; profiling of fecal microbial composition and function; profiling of fecal and serum metabolome; changes in levels of blood glucose, blood lipids, and body mass index; and assessment of adverse events as a measure of safety. DISCUSSION: Expanding upon our previous research on the role of the gut microbiota in the pathogenesis of hypertension, this study serves as a clinical translation advancement and explores the potential of fecal microbiota transplantation for treating hypertension. The underlying mechanisms, particularly the roles of specific microorganisms or their postbiotics in blood pressure amelioration, will also be investigated via multiple approaches, such as metagenomic sequencing and metabolomic profiling. TRIAL REGISTRATION: ClinicalTrials.gov NCT04406129 . Registered on May 28, 2020.

The E3 ubiquitin ligase TRIM31 plays a critical role in hypertensive nephropathy by promoting proteasomal degradation of MAP3K7 in the TGF-ß1 signaling pathway.

Renal fibrosis and inflammation are critical for the initiation and progression of hypertensive renal disease (HRD). However, the signaling mechanisms underlying their induction are poorly understood, and the role of tripartite motif-containing protein 31 (TRIM31), an E3 ubiquitin ligase, in HRD remains unclear. This study aimed to elucidate the role of TRIM31 in the pathogenesis of HRD, discover targets of TRIM31, and explore the underlying mechanisms. Pathological specimens of human HRD kidney were collected and an angiotensin II (AngII)-induced HRD mouse model was developed. We found that TRIM31 was markedly reduced in both human and mouse HRD renal tissues. A TRIM31-/- mice was thus constructed and showed significantly aggravated hypertension-induced renal dysfunction, fibrosis, and inflammation, following chronic AngII infusion compared with TRIM31+/+ mice. In contrast, overexpression of TRIM31 by injecting adeno-associated virus (AAV) 9 into C57BL/6J mice markedly ameliorated renal dysfunction, fibrotic and inflammatory response in AngII-induced HRD relative to AAV-control mice. Mechanistically, TRIM31 interacted with and catalyzed the K48-linked polyubiquitination of lysine 72 on Mitogen-activated protein kinase kinase kinase 7 (MAP3K7), followed by the proteasomal degradation of MAP3K7, which further negatively regulated TGF-ß1-mediated Smad and MAPK/NF-κB signaling pathways. In conclusion, this study has demonstrated for the first time that TRIM31 serves as an important regulator in AngII-induced HRD by promoting MAP3K7 K48-linked polyubiquitination and inhibiting the TGF-ß1 signaling pathway.

A Case Report: An Elderly Male Patient With Takayasu Arteritis After Coronary Artery Bypass Grafting.

Background: Takayasu arteritis is a rare chronic granulomatous inflammation involving the aorta and its main branches. In this report, we describe an extremely rare elderly male patient with Takayasu arteritis (TA) after coronary artery bypass grafting (CABG). Case Summary: A 61-year-old male patient with persistent precordial pain underwent angiography. Vascular murmurs could be heard in carotid artery and bilateral renal artery by auscultation. Laboratory parameters showed high Erythrocyte Sedimentation Rate (ESR) and C-reactive protein (CRP). CT coronary angiography showed multiple stenoses of aorta and its main branches, such as carotid and renal artery involvement. Coronary angiography showed that the coronary artery had multiple branch stenoses, the left anterior descending artery (LAD) had severe stenosis, the distal end of which was reversed to the right coronary artery (RCA), and the RCA was completely occluded. Because of the high level of markers of inflammatory activity, the patient began to take glucocorticoid. Although the patient still had multibranch stenosis of coronary artery, considering the previous CABG operation history, surgery, and interventional therapy of the patient were not feasible, the patient was given conservative drug for further treatment. After treatment, the inflammatory index was significantly descended, and N terminal-pro Brain natriuretic peptide (NT-pro BNP) was decreased. Discussion: A rare case of an elderly male patient with Takayasu arteritis after coronary artery bypass grafting was reported. In addition to hypertension, hyperlipidemia, and other risk factors, coronary artery involvement caused by TA may be a major cause of aggravation of symptoms in patients with acute myocardial infarction (AMI), especially after CABG.