No abstract

Bone marrow derived endothelial progenitor cells (EPCs) are known to play an important role in neovascularization and wound healing. We investigated the temporal effects of cutaneous wounding on EPC surface markers within the peripheral blood (PB) and bone marrow (BM), and better understand the role of the SDF-1α/CXCR4 axis on EPC mobilization after wounding. FVB/NJ mice were administered bilateral 8mm circular full thickness skin wounds. PB and BM were isolated at daily intervals post wounding through day 7 for EPC mobilization characteristics and levels of SDF-1α. Cutaneous wounding was found to cause a transient increase in EPC mobilization that peaked on day 3. In contrast, SDF-1α protein within blood plasma was observed to significantly decrease on days 3, 4, and 7 following cutaneous wounding. BM levels of SDF-1α protein decreased to a nadir on day 3, the same day as peak mobilization was observed to occur. The decrease in BM SDF-1α protein levels was also associated with a decrease in SDF-1α mRNA suggesting transcriptional down regulation as a contributing factor. This study for the first time characterizes EPC mobilization following cutaneous wounding in mice and supports a major role for the SDF-1α/CXCR4 axis in regulating mobilization within the BM, without evidence for systemic increases in SDF-1α.

Abstract-Increased body mass index (BMI) has been correlated with increased blood pressure in human populations. To examine the role of the leptin gene (OB) in essential hypertension in African Americans, we performed affected sib pair analysis on a set of 103 hypertensive African American sibships using four highly polymorphic markers at the human leptin locus. No evidence of linkage was detected between these markers and the phenotype of essential hypertension either in these sibships or in a severely obese subset of 46 sibships in which each sibling had a BMI Ն85th percentile for the US population. Using BMI rather than hypertension as a quantitative trait, we found significant linkage for the marker D7S504 (Pϭ0.029) but not for the other markers. Significance strengthened in the overweight subset of sibships for this marker (Pϭ0.001), and there was a trend of lower P values for the other three markers. However, multipoint analysis with the use of all four markers simultaneously to estimate linkage between BMI and the leptin locus did not demonstrate a statistically significant relationship. Analysis of the coding region of the leptin gene (exons 2 and 3) by single-strand conformational polymorphism revealed a rare Ile-Val polymorphism at amino acid 45 but revealed no other alterations. These results suggest that the OB gene is not a major contributor to the phenotype of essential hypertension in African Americans, although a minor contribution to the phenotype of extreme obesity in this group cannot be ruled out. (Hypertension. 1998;31:1230-1234.)