Advertisement

Cardiovascular Toxicology

, Volume 18, Issue 4, pp 304–311 | Cite as

The Association Between Myocardial Fibrosis and Depressed Capillary Density in Rat Model of Left Ventricular Hypertrophy

  • Ying Xiao
  • Yinjie Liu
  • Jiaming Liu
  • Y. James KangEmail author
Article
  • 330 Downloads

Abstract

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.

Keywords

Myocardial fibrosis Capillaries Left ventricular hypertrophy 

Notes

Acknowledgements

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.

Authors’ Contribution

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.

References

  1. 1.
    Hou, J., & Kang, Y. J. (2012). Regression of pathological cardiac hypertrophy: Signaling pathways and therapeutic targets. Pharmacology & Therapeutics, 135, 337–354.CrossRefGoogle Scholar
  2. 2.
    Ganau, A., Devereux, R. B., Roman, M. J., de Simone, G., Pickering, T. G., Saba, P. S., et al. (1992). Patterns of left ventricular hypertrophy and geometric remodeling in essential hypertension. Journal of the American College of Cardiology, 19, 1550–1558.CrossRefPubMedGoogle Scholar
  3. 3.
    Levy, D., Larson, M. G., Vasan, R. S., Kannel, W. B., & Ho, K. K. (1996). The progression from hypertension to congestive heart failure. JAMA, 275, 1557–1562.CrossRefPubMedGoogle Scholar
  4. 4.
    Zheng, L., Han, P., Liu, J., Li, R., Yin, W., Wang, T., et al. (2015). Role of copper in regression of cardiac hypertrophy. Pharmacology & Therapeutics, 148, 66–84.CrossRefGoogle Scholar
  5. 5.
    Hein, S., Arnon, E., Kostin, S., Schonburg, M., Elsasser, A., Polyakova, V., et al. (2003). Progression from compensated hypertrophy to failure in the pressure-overloaded human heart: Structural deterioration and compensatory mechanisms. Circulation, 107, 984–991.CrossRefPubMedGoogle Scholar
  6. 6.
    Lavine, S. J., & Al, Balbissi K. (2016). Adverse cardiac events and the impaired relaxation left ventricular filling pattern. Journal of the American Society of Echocardiography, 29, 699–708.CrossRefPubMedGoogle Scholar
  7. 7.
    Gao, X. M., Kiriazis, H., Moore, X. L., Feng, X. H., Sheppard, K., Dart, A., et al. (2005). Regression of pressure overload-induced left ventricular hypertrophy in mice. American Journal of Physiology Heart and Circulatory Physiology, 288, H2702–H2707.CrossRefPubMedGoogle Scholar
  8. 8.
    Weber, K. T., & Brilla, C. G. (1991). Pathological hypertrophy and cardiac interstitium. Fibrosis and renin-angiotensin-aldosterone system. Circulation, 83, 1849–1865.CrossRefPubMedGoogle Scholar
  9. 9.
    Ho, C. Y., Lopez, B., Coelho-Filho, O. R., Lakdawala, N. K., Cirino, A. L., Jarolim, P., et al. (2010). Myocardial fibrosis as an early manifestation of hypertrophic cardiomyopathy. New England Journal of Medicine, 363, 552–563.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 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
  11. 11.
    Choudhury, L., Mahrholdt, H., Wagner, A., Choi, K. M., Elliott, M. D., Klocke, F. J., et al. (2002). Myocardial scarring in asymptomatic or mildly symptomatic patients with hypertrophic cardiomyopathy. Journal of the American College of Cardiology, 40, 2156–2164.CrossRefPubMedGoogle Scholar
  12. 12.
    Liu, J., Han, P., Xiao, Y., & Kang, Y. J. (2014). A novel knot method for individually measurable aortic constriction in rats. American Journal of Physiology Heart and Circulatory Physiology, 307, H987–H995.CrossRefPubMedGoogle Scholar
  13. 13.
    Shimizu, T., Narang, N., Chen, P., Yu, B., Knapp, M., Janardanan, J., et al. (2017). Fibroblast deletion of ROCK2 attenuates cardiac hypertrophy, fibrosis, and diastolic dysfunction. JCI Insight, 2, e93187.  https://doi.org/10.1172/jci.insight.93187.CrossRefPubMedCentralGoogle Scholar
  14. 14.
    Jablonowski, R., Fernlund, E., Aletras, A. H., Engblom, H., Heiberg, E., Liuba, P., et al. (2015). Regional stress-induced ischemia in non-fibrotic hypertrophied myocardium in young HCM patients. Pediatric Cardiology, 36, 1662–1669.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Jiang, Y., Reynolds, C., Xiao, C., Feng, W., Zhou, Z., Rodriguez, W., et al. (2007). Dietary copper supplementation reverses hypertrophic cardiomyopathy induced by chronic pressure overload in mice. Journal of Experimental Medicine, 204, 657–666.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 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
  17. 17.
    Xiao, Y., Nie, X., Han, P., Fu, H., & James, Kang Y. (2016). Decreased copper concentrations but increased lysyl oxidase activity in ischemic hearts of rhesus monkeys. Metallomics, 8, 973–980.CrossRefPubMedGoogle Scholar
  18. 18.
    Shinde, A. V., Humeres, C., & Frangogiannis, N. G. (2017). The role of alpha-smooth muscle actin in fibroblast-mediated matrix contraction and remodeling. Biochimica et Biophysica Acta, 1863, 298–309.CrossRefPubMedGoogle Scholar
  19. 19.
    Mihl, C., Dassen, W. R., & Kuipers, H. (2008). Cardiac remodelling: Concentric versus eccentric hypertrophy in strength and endurance athletes. Netherlands Heart Journal, 16, 129–133.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Kong, P., Christia, P., & Frangogiannis, N. G. (2014). The pathogenesis of cardiac fibrosis. Cellular and Molecular Life Sciences, 71, 549–574.CrossRefPubMedGoogle Scholar
  21. 21.
    Talman, V., & Ruskoaho, H. (2016). Cardiac fibrosis in myocardial infarction-from repair and remodeling to regeneration. Cell and Tissue Research, 365, 563–581.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Zhang, W., Zhao, X., Xiao, Y., Chen, J., Han, P., Zhang, J., et al. (2016). The association of depressed angiogenic factors with reduced capillary density in the Rhesus monkey model of myocardial ischemia. Metallomics, 8, 654–662.CrossRefPubMedGoogle Scholar
  23. 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

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  • Ying Xiao
    • 1
  • Yinjie Liu
    • 1
  • Jiaming Liu
    • 1
  • Y. James Kang
    • 1
    Email author
  1. 1.Regenerative Medicine Research Center, West China HospitalSichuan UniversityChengduChina

Personalised recommendations