Microvascular Diameter Responses to the Controlled Release of Platelet Derived Growth Factor‐BB (PDGF‐BB) and Transforming Growth Factor‐β1 (TGF‐β1)

Abstract

PDGF-BB, a smooth muscle cell (SMC) chemoattractant and mitogen, and TGF-β1, a SMC differentiation factor, may have utility as therapeutic arteriogenesis factors. However, few studies have examined whether the controlled release of PDGF-BB or TGF-β1 can amplify arteriogenesis. To this end, we utilized the mouse dorsal skinfold window chamber model, which allows for repeated vessel measurements over time and naturally exhibits arteriolar and venular structural lumen expansion. An 85:15 poly(DL-lactide-co-glycolide) microsphere containing either 0.2μg/mg PDGF-BB, 0.008μg/mg TGF-β1 or 4μg/mg BSA was inserted on Day 7. Microvascular diameter measurements were made at Days 7, 10 and 14 on individual vessels within the release profile of the microsphere (4mm) during topical superfusion of adenosine (10−4 M). Interestingly, PDGF-BB treatment elicited no change in arteriolar structural diameter [PDGF-BB: =25.0μm (48.0%) vs. BSA: =23.1μm (44.2%)], but a significant increase in venular structural diameter [PDGF-BB: =48.9μm (61.9%) vs. BSA: =14.2μm (18.2%)]. TGF-β1 treatment significantly attenuated normal arteriolar [TGFβ1: =7.8μm (17.1%) vs. BSA: =23.1μm (44.2%)] and venular [TGF-β1: =−14.4μm (−1.2%) vs. BSA: =14.2μm (18.2%)] structural lumen expansion. Because PDGF-BB elicited no further increase in arteriolar diameter and TGF-β1 caused vessel constriction, our results do not support the therapeutic potential of these factors. However, the mechanisms of these diameter responses remain unknown, and alterations in growth factor concentration and/or release kinetics may be needed to show efficacy. Supported by NIH HL65958.