PPARG Silencing Improves Blood Pressure Control and Alleviates Renal Damage by Modulating RAS Circadian Rhythm in Hypertensive Rats.

OBJECTIVE: Peroxisome proliferator-activated receptor gamma (PPARG) polymorphisms are associated with hypertension, but the role of PPARG in hypertensive nephropathy is poorly understood. METHODS: Male Sprague-Dawley rats were applied to construct renovascular hypertension model by 2-kid-ney, 1-clip (2K1C) method. Tail vein bolus injection of adeno-associated virus (rAAV)-shPPARG was performed to knockout PPARG in 2K1C rats. The heart rate (HR), systolic pressure (SBP), diastolic pressure (DBP) and activity of rats were monitored after treatments. The role of PPARG in hypertension, renal damage, and circadian rhythm of renin-angiotensin system (RAS) was explored by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), western blot, Masson staining, hematoxylin eosin (HE) staining, Sirius red staining and enzyme-linked immunosorbent assay. RESULTS: PPARG was over-expressed in thoracic aortas of 2K1C rats. 2K1C treatment enhanced DBP and SBP in rats, which was reversed by PPARG silencing. PPARG silencing alleviated 2K1C-induced renal damage. 2K1C treatment reduced angiotensin II and increased angiotensin converting enzyme (ACE) and plasma renin activity (PRA) concentrations in rat plasma during the light period and decreased plasma PRA concentration during the dark period, which were all overturned by PPARG silencing. PPARG silencing effectively improved the RAS circadian rhythm in hypertension. CONCLUSION: PPARG silencing improved blood pressure control and alleviated renal damage by regulating RAS circadian rhythm in hypertensive rats.

Pentraxin 3 depletion (PTX3 KD) inhibited myocardial fibrosis in heart failure after myocardial infarction.

BACKGROUND: HF is a common complication of MI. The underlying mechanisms of myocardial fibrosis in HF after MI are incompletely defined. Here, this study aims to investigate the role of PTX3 KD in HF after MI. METHODS: Bioinformatics analysis based on GSE86569 dataset was performed to explore the potential role of PTX3 in HF. Male C57/BL6J mice were administered with lentiviral vector encoding PTX3 KD or empty vector, and then underwent either coronary ligation or sham surgery. Echocardiography, Masson staining, and immunofluorescence counterstaining were conducted to evaluate the cardiac function and fibrosis. Cardiac fibroblasts were isolated and transfected with lentiviral vector encoding PTX3 KD in vitro to verify the in vivo findings. RESULTS: Bioinformatics analysis based on GSE86569 revealed the aberrant expression of PTX3 in HF patients. Echocardiography showed that PTX3 KD reversed the HF-induced cardiac dysfunction with better cardiac function parameters. Masson staining demonstrated that the obvious infarct and high fibrosis ratio in HF mice were remarkably improved after PTX3 KD. Immunofluorescence staining indicated that the HF-induced increase expression of α-SMA was significantly suppressed by PTX3 KD. Additionally, both in vivo and in vitro results confirmed that PTX3 KD decreased the fibrosis-related up-regulation of collagen I, collagen III, and p-STAT3. However, the result was opposite after IL-6 treatment. CONCLUSIONS: PTX3 KD protects the cardiac function and counteracts the myocardial fibrosis by down-regulating IL-6/STAT3 pathway in HF.

Graft-Versus-Host-Disease of the Central Nervous System and Lung in a Patient With Acute Myeloid Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation: A Case Report.

INTRODUCTION: The common etiology of central nervous system (CNS) complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT) includes CNS infection, metabolic abnormalities, drug toxicity, cerebrovascular events, Epstein-Barr virus-associated posttransplant lymphoproliferative diseases, and hematologic CNS relapse of leukemia. Although graft-versus-host disease (GVHD) is a major complication of allo-HSCT, its CNS involvement is exceedingly rare. CASE PRESENTATION: In this report, we describe a patient who exhibited acute myeloid leukemia with t(8;21) (q22;q22) and who suddenly lost visual acuity ~1 year after receipt of allo-HSCT. Given the observation of negative cerebrospinal fluid findings, cyclosporine-related encephalopathy, intracranial hemorrhage, CNS infection, leukemia recurrence, and tumors were excluded. He was diagnosed with both CNS and pulmonary GVHD. After steroid treatment, the lesions gradually reduced in images acquired via cranial and pulmonary computed tomography. CONCLUSIONS: CNS-GVHD is a rare, serious complication of allo-HSCT that is difficult to diagnose. Biopsy and autopsy may identify the CNS as the target of GVHD in some patients. Treatment is mainly based on the use of immunosuppressive drugs, including high doses of steroids. Early diagnosis and treatment can improve disease outcome.

Prevalence of modifiable risk factors and relation to stroke and death in patients with atrial fibrillation: A report from the China atrial fibrillation registry study.

BACKGROUND: Lifestyle and risk factor management may improve outcomes in patients with atrial fibrillation (AF). We aim to evaluate the prevalence of modifiable risk factors and how these factors impact clinical outcomes in patients with AF. METHODS AND RESULTS: Data on 17 898 AF cohort patients with AF enrolled between 2011 and 2016 was analyzed. A healthy lifestyle was defined as not smoking, not drinking, a healthy body mass index (BMI), untreated total cholesterol less than 200 mg/dL, untreated blood pressure (BP) less than 120/80 mm Hg, and untreated fasting plasma glucose (FPG) less than 100 mg/dL. The association between risk factors and risk of the composite endpoint of all-cause mortality and nonfatal ischemic stroke were assessed using Cox proportional hazards regression model. Only 4.0% of patients achieved a healthy lifestyle. In multivariate analysis, current smoking, a low BMI, not well-controlled FPG were independently and significantly associated with higher risk of all-cause mortality and nonfatal ischemic stroke, with corresponding hazard ratio (HR) estimates 1.22 (95% confidence interval [CI], 1.00-1.47), HR = 1.72 (95% CI, 1.34-2.20), and HR = 1.25 (95% CI, 1.06-1.46), respectively. High BP was also associated with higher risk with the outcomes (HR = 1.15, 95% CI, 1.00-1.34). Compared with patients with no risk factor, those who failed to maintained or achieved optimal risk factor control had a progressively higher risk of death and nonfatal ischemic stroke (HR for 1 risk factor = 1.44; 95% CI, 1.07-1.92; and more than 2 risk factors = 1.75; 95% CI, 0.99-3.09). CONCLUSIONS: Maintenance of well-controlled risk factors may substantially lower the risk of death and ischemic stroke in patients with AF.

Effects of Dual-Dose Clopidogrel, Clopidogrel Combined with Tongxinluo Capsule, and Ticagrelor on Patients with Coronary Heart Disease and CYP2C19*2 Gene Mutation After Percutaneous Coronary Interventions (PCI).

BACKGROUND In recent years, genetic factors have attracted research interest as important predisposing factors for cardiovascular susceptibility. This study aimed to investigate the influences of dual-dose clopidogrel, clopidogrel combined with tongxinluo, and ticagrelor on the platelet activity and MACE events of patients with CYP2C19*2 gene function deficiency and poor clopidogrel response after PCI. MATERIAL AND METHODS We selected 458 patients with coronary heart disease undergoing PCI, and the genotype of CYP2C19*2 was detected by TaqMan real-time PCR. We finally enrolled 212 patients and divided them into 4 groups: a standard anti-platelet group of 46 patients, a clopidogrel double-dose group of 50 cases, a clopidogrel combined with tongxinluo group of 59 cases, and a ticagrelor group of 57. The platelet inhibition rate was detected by TEG. We analyzed and compared differences in platelet activity and the occurrence of MACE events in these 4 groups at different follow-up times. RESULTS The results showed that inhibition of platelet aggregation was better in the double-dose clopidogrel group, the clopidogrel combined with tongxinluo group, and the ticagrelor group than in the regular-dose clopidogrel group, and ticagrelor was the best. We also found that the total incidence of MACE was much lower in the double-dose clopidogrel group, the clopidogrel combined with tongxinluo group, and the ticagrelor group, while the incidence of hemorrhage in the ticagrelor group was higher. CONCLUSIONS Adjusting the dose or combining with other drugs improves the efficacy of anti-platelet therapy and reduces the incidence of ischemic events after PCI.