Accelerated Decline in Circulating Progenitor Cells Due to Aldosterone Excess in Experimental Hypertension

Abstract

Introduction: Bone marrow-derived progenitor cells may have a reparative and thus potentially therapeutic role in cardiovascular disease. Reduced reparative progenitor cell production or function may play a role in hypertension related vascular injury. Further, in vitro studies suggest that humoral activation (aldosterone) impairs production of progenitor cells, potentially limiting endogenous repair mechanisms and accelerating vascular damage during the transition to heart failure. Hypothesis: We hypothesized that circulating progenitor cells would be depleted in vivo in response to experimental hypertension and that these changes would be accelerated in the presence of concomitant aldosterone excess. Methods: Ten dogs underwent renal wrapping (RW) to induce hypertension. Blood pressure (BP) was measured weekly. After development of hypertension (5 weeks after RW), dogs were randomized to receive deoxycorticosterone acetate (1mg/kg/day for 3 weeks; HTN + DOCA) or not (HTN). Flow cytometric analysis for CD34+ (progenitor) cells was performed on whole blood harvested prior to and every 2 weeks after RW. ISHAGE criteria were used to enumerate CD34+ cells. Results: See Figure. Dogs were similarly hypertensive at 5 weeks; BP increased week 5-8 only in HTN + DOCA dogs. The CD34+ cell counts were similar prior to RW and decreased over time after RW in both groups. However, the decline in CD34+ cells was accelerated in the HTN + DOCA dogs after DOCA treatment. Conclusion: This study demonstrates a progressive decrease in circulating progenitor cells over time after the onset of experimental hypertension. This may represent impaired bone marrow production or homing to sites of hypertension related vascular injury. However, the dramatic drop in CD34+ cells after DOCA administration is consistent with the previous in vitro studies suggesting that aldosterone impairs bone marrow derived progenitor cell formation. These data support the concept that humoral activation accelerates vascular injury by limiting endogenous reparative mechanisms.