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Enhanced Acute Responses to Inflammatory Stimuli at Early Stage of Microvessel Remodeling
Author(s) -
Yuan Dong,
Zhou Xueping,
He Pingnian
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.975.11
Subject(s) - microvessel , inflammation , basal (medicine) , phalloidin , pathology , platelet activating factor , vascular permeability , angiogenesis , neovascularization , endothelium , chemistry , medicine , endocrinology , cell , cytoskeleton , biochemistry , insulin
Vascular remodeling has been implicated in many chronic inflammatory diseases. This study aims to investigate the impact of chronic inflammation‐induced vascular remodeling on the acute venular responses to inflammatory mediators. Experiments were conducted in mesenteric venules using a survival rat model. Microvessel permeability was determined by Lp measurements and changes in VE‐Cadherin and F‐actin were viewed with confocal images. In day 1, basal and platelet activating factor (PAF, 10 nM) stimulated Lp were measured in individually perfused venules under aseptic conditions. Then blood flow was resumed in the perfused vessel and rat was recovered from anesthesia. In day 3, the baseline Lp measured in the same vessel showed no significant changes from day 1, but vessel diameters increased 74 ± 8 % (n = 8). When each vessel was exposed to PAF, the mean peak Lp reached 5.1 ± 1.2 times that of the response in Day 1. VE‐Cadherin staining at Lp peak showed frequent breaks with apparent gaps between endothelial cells (ECs), a pattern different from that observed in day 1. Phalloidin staining showed disorganized and fragmented F‐actin in both ECs and pericytes. The venular intercellular junctions per circumference in day 1 showed no significant difference from the enlarged venules in day 3, indicating no increases in EC number. Our results demonstrated that the observed morphological changes 3 days after the initial stimulation did not change the basal Lp, but manifested augmented acute response to PAF, indicating that the cellular phenotype at early stage of vascular remodeling are capable of mediating acute exacerbated vascular dysfunction upon additional stimulation. Supported by HL56237 and HL084338.