Frame Mary D, Lin Fubao, Dewar Anthony M, Clark Richard A F
Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, USA.
Department of Physiology and Biophysics, Stony Brook University, Stony Brook, NY, USA.
Microcirculation. 2017 Aug;24(6). doi: 10.1111/micc.12369.
Following thermal burn injury, plasma fibronectin degrades within the interstitium; one possible product is EVA-1, PSHISKYILRWRPK found within the FNIII . EVA-1 ameliorates thermal burn injury progression, and binds to and enhances PDGF-BB in promoting cell metabolism, growth and survival; shorter related peptides lose these abilities. Here we study the effect of EVA-1 and shorter peptides for their vasoactivity under quiescent and stress conditions.
Using the hamster cheek pouch intravital microscopy model, five EVA-1 related peptides were applied to small arterioles via micropipette (10 -10 mol L ) in quiescent tissue and after defined stress: nitric oxide or heat.
Peak dilation occurred with nanomolar doses (longer peptides) or below (shorter peptides), blocked by propranolol (beta-adrenergic receptor antagonist). Micromolar doses of the same peptides induced only constriction, not antagonized by phentolamine (alpha-adrenergic receptor antagonist). Scrambled variants of two peptides yielded only constriction, suggesting constriction might be due peptide charge. Each stressor caused a left shift in dilation response, blocked by carazolol.
Thus, this important region of FNIII contains sequences that have a gradation of biological functions dependent on the length of the peptide sequence, with increased efficacy for dilation following stressors.
热烧伤后，血浆纤连蛋白在间质中降解；一种可能的产物是EVA-1，即FNIII内发现的PSHISKYILRWRPK。EVA-1可改善热烧伤的进展，并在促进细胞代谢、生长和存活方面与血小板衍生生长因子-BB（PDGF-BB）结合并增强其作用；较短的相关肽则失去这些能力。在此，我们研究EVA-1和较短肽在静态和应激条件下的血管活性作用。
使用仓鼠颊囊活体显微镜模型，通过微量移液器将五种与EVA-1相关的肽以10 -10 mol/L的浓度应用于静态组织中的小动脉以及在特定应激（一氧化氮或热）后。
纳摩尔剂量（较长肽）或更低剂量（较短肽）时出现最大扩张，普萘洛尔（β-肾上腺素能受体拮抗剂）可阻断该扩张。相同肽的微摩尔剂量仅诱导收缩，酚妥拉明（α-肾上腺素能受体拮抗剂）不能拮抗该收缩。两种肽的乱序变体仅产生收缩，提示收缩可能归因于肽的电荷。每种应激源均导致扩张反应向左移位，卡拉洛尔可阻断该移位。
因此，FNIII的这一重要区域包含一些序列，其生物学功能因肽序列长度而异，应激源作用后扩张效力增强。
