Pole of Pharmacology, Université catholique de Louvain (UCL), Avenue Emmanuel Mounier 53 box B1.53.09, 1200, Brussels, Belgium.
Angiogenesis. 2012 Dec;15(4):581-92. doi: 10.1007/s10456-012-9282-0. Epub 2012 Jun 3.
Wounds notoriously accumulate lactate as a consequence of both anaerobic and aerobic glycolysis following microcirculation disruption, immune activation, and increased cell proliferation. Several pieces of evidence suggest that lactate actively participates in the healing process through the activation of several molecular pathways that collectively promote angiogenesis. Lactate indeed stimulates endothelial cell migration and tube formation in vitro, as well as the recruitment of circulating vascular progenitor cells and vascular morphogenesis in vivo. In this study, we examined whether the pro-angiogenic potential of lactate may be exploited therapeutically to accelerate wound healing. We show that lactate delivered from a Matrigel matrix improves reperfusion and opposes muscular atrophy in ischemic hindlimb wounds in mice. Both responses involve lactate-induced reparative angiogenesis. Using microdialysis and enzymatic measurements, we found that, contrary to poly-L-lactide (PLA), a subcutaneous implant of poly-D,L-lactide-co-glycolide (PLGA) allows sustained local and systemic lactate release. PLGA promoted angiogenesis and accelerated the closure of excisional skin wounds in different mouse strains. This polymer is FDA-approved for other applications, emphasizing the possibility of exploiting PLGA therapeutically to improve wound healing.
创伤后，微循环障碍、免疫激活和细胞增殖会导致糖酵解（包括无氧糖酵解和有氧糖酵解），从而使创伤处堆积乳酸。有多项证据表明，乳酸通过激活多种分子途径积极参与愈合过程，这些途径共同促进血管生成。乳酸确实能刺激体外内皮细胞迁移和管状结构形成，并促进体内循环血管祖细胞募集和血管形态发生。在这项研究中，我们研究了乳酸的促血管生成潜力是否可被用于治疗以加速伤口愈合。我们发现，从 Matrigel 基质中释放的乳酸可改善缺血性后肢伤口的再灌注，并对抗肌肉萎缩。这两种反应都涉及乳酸诱导的修复性血管生成。通过微透析和酶测量，我们发现，与聚 L-乳酸（PLA）相反，聚 D,L-乳酸-共-乙醇酸（PLGA）的皮下植入物可实现持续的局部和全身乳酸释放。PLGA 促进了血管生成，并加速了不同小鼠品系的皮肤切除伤口的闭合。该聚合物已获得 FDA 批准用于其他应用，这强调了利用 PLGA 进行治疗以改善伤口愈合的可能性。
