Chronic remote ischemic preconditioning-induced increase of circulating hSDF-1α level and its relation with reduction of blood pressure and protection endothelial function in hypertension.

Although previous data showed that remote ischemic preconditioning (RIPC) has beneficial effect on blood pressure (BP) reduction, the efficacy of RIPC-induced decline in BP and the favorable humoral factors in hypertension is elusive. This present study is performed to evaluate whether RIPC reduces BP, improves microvascular endothelial function and increases circulating hSDF-1α generation in hypertension. Fifteen hypertensive patients received 3 periods of 5-min inflation/deflation of the forearm with a cuff on the upper arm daily for 30 days. Clinic and 24-h ambulatory blood pressure monitoring (ABPM) were examined before and after the end of this procedure. Microvascular endothelial function was measured by finger reactive hyperemia index (RHI) using the Endo-PAT 2000 device. The circulating hSDF-1α level was tested by ELISA. RIPC significantly decreased systolic BP (139.13 ± 6.68 versus 131.45 ± 7.45 mmHg) and diastolic BP (89.67 ± 4.98 versus 83.83 ± 6.65 mmHg), meanwhile 24-h ambulatory systolic and diastolic BP dropped from 136.33 ± 9.10 mmHg to 131.33 ± 7.12 mmHg and 87.60 ± 6.22 mmHg to 82.47 ± 4.47 mmHg respectively. RHI was improved (1.95 ± 0.34 versus 2.47 ± 0.44). Plasma hSDF-1α level was markedly increased after RIPC (1585.86 ± 167.17 versus 1719.54 ± 211.17 pg/ml). The increase in hSDF-1α level was associated with the fall in clinic and 24-h ABPM and rise in RHI. The present data suggests that RIPC may be a novel alternative or complementary intervention means to treat hypertension and protect endothelial function.

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: Berberinemodified 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.