The Association Between Myocardial Fibrosis and Depressed Capillary Density in Rat Model of Left Ventricular Hypertrophy
- 330 Downloads
Myocardial fibrogenesis is initiated once the coordination between oxygen supply and demand is disrupted in pressure overload-induced cardiac hypertrophy. Clinical observations showed that myocardial fibrosis did not evenly occur in the hypertrophic myocardium. The present study was undertaken to specifically address differential vulnerabilities to fibrogenesis of different regions in the myocardium subjected to pressure overload-induced hypertrophy. SD rats were divided into two groups, sham-operated control and ascending artery constriction-induced cardiac hypotrophy. Thirty-four weeks after surgery, rats were sacrificed and hearts were harvested. Myocardial tissues were processed and sequentially sectioned for detection of collagen deposition, myocyte hypertrophy and vascular density analysis. Redundant collagen stained with Sirius red and anti-collagen I antibody was found in the extracellular matrix, but high volume of collagen fraction was largely localized more in posterior and lateral walls than in anterior wall and interventricular septum, which is in accordance with the accumulation of fibroblasts. In association with the differential regional collagen accumulation, the cardiomyocytes were more hypertrophic in the posterior and lateral wall than the other left ventricle. However, the capillary density in the lateral and posterior walls was significantly decreased. The results indicated that the posterior and lateral walls were more vulnerable to fibrogenesis post-pressure overload-induced cardiac hypertrophy, which was associated with the depressed angiogenesis in these two regions.
KeywordsMyocardial fibrosis Capillaries Left ventricular hypertrophy
This work was supported by National Science Foundation of China (Grant Number 81230004 to Y. J. Kang).The authors thank Xiaorong Sun, Ning Wang and Lin Bai for technical support.
All authors participated in the design and review of this work; YX carried out the HE, Sirius red and immunofluorescent staining, data collection and statistical analysis; YL and JL performed the animal surgery, echocardiography and data collection; YX and YL analyzed the data and interpreted the results; YX wrote the draft of the manuscript; and YJK edited, revised and approved the final version of the manuscript.
Compliance with Ethical Standards
Conflicts of interest
All author report no conflicts of interest.
- 10.Shiozaki, A. A., Senra, T., Arteaga, E., Martinelli, Filho M., Pita, C. G., Avila, L. F., et al. (2013). Myocardial fibrosis detected by cardiac CT predicts ventricular fibrillation/ventricular tachycardia events in patients with hypertrophic cardiomyopathy. Journal of Cardiovascular Computed Tomography, 7, 173–181.CrossRefPubMedPubMedCentralGoogle Scholar
- 16.Condorelli, G., Morisco, C., Stassi, G., Notte, A., Farina, F., Sgaramella, G., et al. (1999). Increased cardiomyocyte apoptosis and changes in proapoptotic and antiapoptotic genes bax and bcl-2 during left ventricular adaptations to chronic pressure overload in the rat. Circulation, 99, 3071–3078.CrossRefPubMedGoogle Scholar
- 23.Xie, Y., Chen, J., Han, P., Yang, P., Hou, J., & Kang, Y. J. (2012). Immunohistochemical detection of differentially localized up-regulation of lysyl oxidase and down-regulation of matrix metalloproteinase-1 in rhesus monkey model of chronic myocardial infarction. Experimental Biology and Medicine (Maywood, NJ), 237, 853–859.CrossRefGoogle Scholar