NAD^(+) exhaustion by CD38 upregulation contributes to blood pressuree elevation and vascular damage in hypertension

Hypertension is characterized by endothelial dysfunction and arterial stiffness,which contribute to the pathogenesis of atherosclerotic cardiovascular diseases.Nicotinamide adenine dinucleotide(NAD^(+))is an indispensable cofactor in all living cells that is involved in fundamental biological processes.However,in hypertensive patients,alterations in NAD^(+)levels and their relation with blood pressure(BP)elevation and vascular damage have not yet been studied.

Berberine-Promoted CXCR4 Expression Accelerates Endothelial Repair Capacity of Early Endothelial Progenitor Cells in Persons with Prehypertension

Objective： To evaluate whether the berberine treatment can improve endothelial repair capacity of early endothelial progenitor cells （EPCs） from prehypertensive subjects through increasing CXC chemokine receptor 4 （CXCR4） signaling. Methods： EPCs were isolated from prehypertensive and healthy subjects and cultured. In vivo reendothelialization capacity of EPCs from prehypertensive patients with or without in vitro berberine treatment was examined in a nude mouse model of carotid artery injury. The protein expressions of CXCR4/Janus kinase-2 （JAK-2） signaling of in vitro EPCs were detected by Western blot analysis. Results： CXCR4 signaling and alteration in migration and adhesion functions of EPCs were evaluated. Basal CXCR4 expression was significantly reduced in EPCs from prehypertensive patients compared with normal subjects （P〈0.01）. Also, the phosphorylation of JAK-2 of EPCs, a CXCR4 downstream signaling, was significantly decreased （P〈0.01）. Berberine promoted CXCR4/JAK-2 signaling expression of in vitro EPCs （P〈0.01）. Transplantation of EPCs pretreated with berberine markedly accelerated in vivo reendothelialization （P〈0.01）. The increased in vitro function and in vivo reendothelialization capacity of EPCs were inhibited by CXCR4 neutralizing antibody or pretreatment with JAK-2 inhibitor AG490, respectively （P〈0.01）. Conclusion： Berberine- modified EPCs via up-regulation of CXCR4 signaling contributes to enhanced endothelial repair capacity in prehypertension, indicating that berberine may be used as a novel potential primary prevention means against prehypertension-related atherosclerotic cardiovascular disease.

Predictive value of neutrophil-to-lymphocyte ratio on drug eluting stent restenosis in patients with type 2 diabetes mellitus

Despite major advances achieved in percutaneous coronary intervention(PCI)and antithrombotic therapies,in-stent restenosis(ISR)is still a challenging clinical problem after PCI.It is very important to identify a new parameter for ISR risk stratification and as potential pharmacological targets.We previously reviewed that Neutrophil-to-lymphocyte ratio(NLR)may be the best predictor of ISR among several parameters of blood cells.Type 2 diabetes mellitus(T2DM)is closely related to inflammation and acts as an independent risk factor of ISR.However,few studies have evaluated the predictive role of the dynamic changes of NLR on ISR in patients with T2DM.Therefore,we aimed to analyze preprocedural NLR value in the first PCI and the second coronary angiography(CAG),and evaluate its predictive value on ISR in patients with T2DM.