title: Vascular rhexis: loss of integrity of coronary vasculature in mice subjected to myocardial infarction.
abstract: We previously observed gross hemorrhage in plasminogen activator inhibitor type-1 (PAI-1) knockout (PKO) mice with induced myocardial infarction (MI). We hypothesized that it reflected degradation of vessels - a phenomenon we termed vascular rhexis. Accordingly, in the present study we characterized vascular rhexis in C57BL6 mice. MI was induced in 10- to 12-week-old mice by coronary artery ligation for 24, 48, 72 or 96 h. Hemorrhage was quantified by non-cross-reacting enzyme-linked immunosorbent assay of left ventricular (LV) hemoglobin corrected for myoglobin. Degradation of vasculature was quantified by the appearance of alpha smooth muscle actin (alphaSMA) in low salt soluble fractions of LV homogenates (Western blotting) and by immunohistochemistry (residual alphaSMA). Co-staining for CD31 (endothelial cells) and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) (a marker of cell death) was used to identify capillary rhexis. PKO mice (n = 9) had marked hemorrhage in infarct zones (432 +/- 27 standard error of mean microL blood/g). Hemorrhage was evident in C57BL6 mice as well (n = 6): 51 +/- 8 microL/g LV 96 h after coronary occlusion compared with 10 +/- 5 microL /g, n = 13 in normal LVs. Residual intact vasculature was reduced 48 h after infarction. Thus, an average of 16 +/- 1.6 small- and medium-sized vessels (n = 5 hearts) were seen compared with 84 +/- 4.8 in normal LVs (n = 3, P < or = 0.05). An approximately three-fold increase in soluble alphaSMA 48 h after MI (2.68 +/- 0.28, n = 6) was seen relative to that in normal LVs defined as 1.0 +/- 0.04, n = 10, P < or = 0.05. Capillary degradation was evident as well, as judged from CD31 and TUNEL co-localization. Vascular rhexis occurs within 48 h after the onset of MI. It may contribute to the early no-reflow phenomenon and to late negative LV remodeling.
authors.affiliation: Department of Medicine, Cardiovascular Research Institute, University of Vermont, Colchester, 05446, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: French
authors.forename: A K M T
authors.initials: AK
authors.lastname: Zaman
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Kelm
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Spees
authors.forename: Burton E
authors.initials: BE
authors.lastname: Sobel
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D004797:Enzyme-Linked Immunosorbent Assay; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology; D006470:Hemorrhage / Q000378:metabolism; D007150:Immunohistochemistry; D007511:Ischemia / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation / Q000502:physiology; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D018919:Neovascularization, Physiologic; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D013997:Time Factors; D018487:Ventricular Dysfunction, Left; D020257:Ventricular Remodeling
chemical_list: D017395:Plasminogen Activator Inhibitor 1