Background: The morning blood pressure surge (MBPS) is related to an exaggerated risk of cardiovascular diseases and mortality. With increasing attention on circadian change in blood pressure and extensive use of ambulatory blood pressure monitoring (ABPM), chronotherapy that administration of medication according to biological rhythm, is reported to improve cardiovascular outcomes. The aim of this study is to evaluate the influence of chronotherapy of antihypertensive drugs upon MBPS in hypertensive patients.Methods: A search strategy was applied in Ovid MEDLINE, EMBASE, Cochrane (Wiley) CENTRAL Register of Controlled Trials, Cochrane Database of Systematic Reviews, and the Chinese Biomedical literature database. No language and date restrictions. Randomized controlled trials (RCT) assessing the efficacy of evening and morning administration of the same medications in adult patients with primary hypertension were included.Results: A total of ten trials, comprising 1724 participants with a mean age of 61 and 51% female, were included in this study. Combined analysis observed significant reduction of MBPS (− 5.30 mmHg, 95% CI − 8.80 to − 1.80), night-time SBP (− 2.29 mmHg, 95% CI − 4.43 to − 0.15), night-time DBP (− 1.63 mmHg, 95 %CI − 3.23 to − 0.04) and increase in night blood pressure dipping (3.23%, 95% CI 5.37 to 1.10) in evening dosage compared with traditional morning dosage of blood pressure-lowering drugs. No significant difference was found in the incidence of overall adverse effects (RR 0.65, 95% CI 0.30 to 1.41) and withdrawal due to adverse effects (RR 0.95, 95% CI 0.53 to 1.71).Conclusions: Our study suggested that evening administration of antihypertensive medications exerted better blood pressure-lowering effect on MBPS compared with conventional morning dosage. Safety assessment also indicated that the evening regimen did not increase the risk of adverse events. However, endpoint studies need to be carried out to confirm the significance and feasibility of this treatment regimen in clinical practice.

Vascular remodeling is a pathological basis of various disorders. Therefore, it is necessary to understand the occurrence, prevention, and treatment of vascular remodeling. Krüppel-like factor 5 (KLF5) has been identified as a significant factor in cardiovascular diseases during the last two decades. This review provides a mechanism network of function and regulation of KLF5 in vascular remodeling based on newly published data and gives a summary of its potential therapeutic applications. KLF5 modulates numerous biological processes, which play essential parts in the development of vascular remodeling, such as cell proliferation, phenotype switch, extracellular matrix deposition, inflammation, and angiogenesis by altering downstream genes and signaling pathways. Considering its essential functions, KLF5 could be developed as a potent therapeutic target in vascular disorders.

Background: Smoking cessation was associated with improved prognosis of coronary artery disease. This study was designed to investigate the effect of smoking cessation on high-density lipoprotein functionality in coronary artery disease patients. Methods: In this prospective, randomized and parallel controlled study, coronary artery disease smokers ( n = 28) and healthy smokers ( n = 30) were divided into smoking cessation group and continuous smoking group, respectively. Blood samples were collected before and after three-month smoking cessation. Plasma high-density lipoprotein was isolated by density gradient centrifugation. The ability of high-density lipoprotein against copper-induced oxidation of lipoprotein was determined to evaluate the antioxidative property of high-density lipoprotein, and the macrophage migration inhibited by high-density lipoprotein was tested to identify the antichemotactic property of high-density lipoprotein. High-density lipoprotein-induced macrophage cholesterol efflux was measured by fluorescence spectrometry using NBD cholesterol analogue. Healthy non-smoking volunteers were enrolled as the baseline control. Results: The baseline antioxidative, antichemotactic ability of high-density lipoprotein and high-density lipoprotein-induced cellular cholesterol efflux in coronary artery disease smokers and healthy smokers were significantly attenuated when compared with those in healthy non-smokers. After three-month smoking cessation, both the antioxidative ability and antichemotactic ability of high-density lipoprotein were improved significantly in coronary artery disease smokers. However, high-density lipoprotein-induced cellular cholesterol efflux was not increased by smoking cessation. In in vitro experiments, carbon monoxide reduced the antioxidative ability and nicotine enhanced the antichemotactic ability of high-density lipoprotein. Conclusions: Smoking cessation is an effective measure to improve high-density lipoprotein functions in coronary artery disease smokers. Our study re-emphasizes the importance of smoking cessation in the secondary prevention of coronary artery disease.

Aims: To investigate cardiac pathology in critically ill patients with coronavirus disease 2019 (COVID-19) and identify associations between pathological changes and clinical characteristics.Methods: The present autopsy cohort study included hearts from 26 deceased patients hospitalized in intensive care units due to COVID-19, and was conducted at four sites in Wuhan, China. Cases were divided into a neutrophil infiltration group and a no-neutrophil group based on the presence or absence of histopathologically identified neutrophilic infiltrates.Results: Among the 26 patients, histopathological examination identified active myocarditis in four patients. All patients with myocarditis exhibited extensive accompanying neutrophil infiltration, and all patients without myocarditis did not. The neutrophil infiltration group exhibited significantly higher rates of detection of interleukin-6 (100 vs. 4.6%) and tumor necrosis factor-alpha (100 vs. 31.8%) than the no-neutrophil group (both p < 0.05). On admission, four patients with neutrophil infiltration in myocardium had significantly higher baseline levels of aspartate aminotransferase, D dimer, and high-sensitivity C reactive protein than the other 22 patients (all p < 0.05). During hospitalization, patients with neutrophil infiltration had significantly higher maximum creatine kinase-MB (median 280.0 IU/L vs. 38.7 IU/L, p = 0.04) and higher troponin I (median 1.112 ng/ml vs. 0.220 ng/ml, p = 0.56) than patients without neutrophil infiltration.Conclusion: Active myocarditis was frequently associated with neutrophil infiltration in the hearts of deceased patients with severe COVID-19. Patients with neutrophil-infiltrated myocarditis had a series of severely abnormal laboratory test results on admission, and high maximum creatine kinase-MB during hospitalization. The role of neutrophils in severe heart injury and systemic conditions in patients with COVID-19 should be emphasized.

Salt-sensitive hypertension is closely related to inflammation, but the mechanism is barely known. Transmembrane member 16A (TMEM16A) is the Ca²⁺-activated chloride channel in epithelial cells, smooth muscle cells, and sensory neurons. It can promote inflammatory responses by increasing proinflammatory cytokine release. Here, we identified a positive role of TMEM16A in vascular inflammation. The expression of TMEM16A was increased in high-salt-stimulated vascular smooth muscle cells (VSMCs), whereas inhibiting TMEM16A or silencing TMEM16A with small interfering RNA (siRNA) can abolish this effect in vitro or in vivo. Transcriptome analysis of VSMCs revealed some differential downstream genes of TMEM16A related to inflammation, such as endothelial cell-specific molecule 1 (ESM1) and CXC chemokine ligand 16 (CXCL16). Overexpression of TMEM16A in VSMCs was accompanied by high levels of ESM1, CXCL16, intercellular adhesion molecule-1 (ICAM-1), and vascular adhesion molecule-1 (VCAM-1). We treated VSMCs cultured with high salt and arctigenin (ARC), T16Ainh-A01 (T16), and TMEM16A siRNA (siTMEM16A), leading to greatly decreased ESM1, CXCL16, VCAM-1, and ICAM-1. Beyond that, silencing ESM1, the expression of VCAM-1 and ICAM-1, and CXCL16 was attenuated. In conclusion, our results outlined a signaling scheme that increased TMEM16 protein upregulated ESM1, which possibly activated the CXCL16 pathway and increased VCAM-1 and ICAM-1 expression, which drives VSMC inflammation. Beyond that, arctigenin, as a natural inhibitor of TMEM16A, can reduce the systolic blood pressure (SBP) of salt-sensitive hypertension mice and alleviate vascular inflammation.