Nourian Zahra, Hong Kwangseok, Li Min, Castorena-Gonzalez Jorge A, Martinez-Lemus Luis A, Clifford Philip S, Meininger Gerald A, Hill Michael A
Dalton Cardiovascular Research Center, Columbia, MO, United States.
Department of Medical Pharmacology and Physiology and University of Missouri, Columbia, MO, United States.
Front Pharmacol. 2023 Aug 15;14:1210128. doi: 10.3389/fphar.2023.1210128. eCollection 2023.
Vascular extracellular matrix (ECM) is dominated by elastic fibers (elastin with fibrillin-rich microfibrils) and collagens. Current understanding of ECM protein development largely comes from studies of conduit vessels (e.g., aorta) while resistance vessel data are sparse. With an emphasis on elastin, we examined whether changes in postnatal expression of arteriolar wall ECM would correlate with development of local vasoregulatory mechanisms such as the myogenic response and endothelium-dependent dilation. Rat cerebral and mesenteric arteries were isolated at ages 3, 7, 11, 14, 19 days, 2 months, and 2 years. Using qPCR mRNA expression patterns were examined for elastin, collagen types I, II, III, IV, fibrillin-1, and -2, lysyl oxidase (LOX), and transglutaminase 2. Elastin, LOX and fibrillar collagens I and III mRNA peaked at day 11-14 in both vasculatures before declining at later time-points. 3D confocal imaging for elastin showed continuous remodeling in the adventitia and the internal elastic lamina for both cerebral and mesenteric vessels. Myogenic responsiveness in cannulated cerebral arteries was detectable at day 3 with constriction shifted to higher intraluminal pressures by day 19. Myogenic responsiveness of mesenteric vessels appeared fully developed by day 3. Functional studies were performed to investigate developmental changes in endothelial-dependent dilation. Endothelial-dependent dilation to acetylcholine was less at day 3 compared to day 19 and at day 3 lacked an endothelial-derived hyperpolarizing factor component that was evident at day 19. Collectively, in the rat small artery structural remodeling and aspects of functional control continue to develop in the immediate postnatal period.
血管细胞外基质（ECM）主要由弹性纤维（含富含原纤蛋白的微原纤维的弹性蛋白）和胶原蛋白组成。目前对ECM蛋白发育的理解主要来自对输送血管（如主动脉）的研究，而关于阻力血管的数据则很稀少。以弹性蛋白为重点，我们研究了小动脉壁ECM出生后表达的变化是否与局部血管调节机制（如肌源性反应和内皮依赖性舒张）的发育相关。在3、7、11、14、19天、2个月和2岁时分离大鼠脑动脉和肠系膜动脉。使用qPCR检测弹性蛋白、I、II、III、IV型胶原蛋白、原纤蛋白-1和-2、赖氨酰氧化酶（LOX）和转谷氨酰胺酶2的mRNA表达模式。弹性蛋白、LOX以及I型和III型纤维状胶原蛋白的mRNA在两种血管中均在第11 - 14天达到峰值，随后在后期时间点下降。弹性蛋白的三维共聚焦成像显示，脑动脉和肠系膜血管的外膜和内弹性膜均持续重塑。插管脑动脉的肌源性反应在第3天即可检测到，到第19天收缩转移到更高的腔内压力。肠系膜血管的肌源性反应在第3天似乎已完全发育。进行功能研究以调查内皮依赖性舒张的发育变化。与第19天相比，第3天对乙酰胆碱的内皮依赖性舒张作用较小，且第3天缺乏第19天明显存在的内皮衍生超极化因子成分。总体而言，在大鼠小动脉中，结构重塑和功能控制方面在出生后即刻仍在继续发育。
