Expressions of CD11a, CD11b, and CD11c integrin proteins in rats with myocardial hypertrophy

Document Type: Original Article


1 Morphological Laboratory of Xinxiang Medical University, Xinxiang, Henan 453003, P. R. China

2 Life Science and Technology Department, Xinxiang Medical University, Xinxiang, Henan 453003, P. R. China

3 Key Open Laboratory for Tissue Regeneration of Henan Providence, Xinxiang, Henan 453003, P. R. China


Objective(s):To examine the expressions of CD11a, CD11b, and CD11c integrins in the myocardial tissues of rats with isoproterenol-induced myocardial hypertrophy. This study also provided morphological data to investigate the signal transduction mechanisms of myocardial hypertrophy and reverse it.
Materials and Methods: A myocardial hypertrophy model was established by subcutaneously injecting isoprenaline in healthy adult Sprague-Dawley rats. Myocardial tissues were obtained, embedded in conventional paraffin, sectioned, and stained with hematoxylin. Pathological changes in myocardial tissues were then observed. The expressions and distributions of CD11a, CD11b, and CD11c integrins were detected by immunohistochemistry. Changes in the mRNA expressions of CD11a, CD11b, and CD11c in the myocardial tissues of rats were detected by RT-PCR. Image analysis software was used to determine the expressions of CD11a, CD11b, and CD11c integrins quantitatively.
Results: Immunohistochemical results showed that the positive expressions of CD11a, CD11b, and CD11c integrins increased significantly in the experimental group compared with those in the control group. The mRNA expressions of CD11a, CD11b, and CD11c in the myocardial tissues of rats were consistent with the immunohistochemical results.
Conclusion: The increase in the protein expressions of CD11a, CD11b, and CD11c integrins may have an important role in the occurrence and development of myocardial hypertrophy.


1. Dickstein K, Cohen-Solal A, Filippatos G, McMurray JJ, Ponikowski P, Poole-Wilson PA, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the task force for the diagnosis and treatment of acute and chronic heart failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur Heart J 2008; 10:933-989.

2. Bettink SI, Werner C, Chen CH, Muller P, Schirmer SH, Walenta KL, et al. Integrin-linked kinase is a central mediator in angiotensin II type 1- and chemokine receptor CXCR4 signaling in myocardial hypertrophy. Biochem Biophys Res Commun 2010; 397:208-213.

3. Swynghedauw B, Delcayre C, Samuel JL, Mebazaa A, Cohen-Solal A. Molecular mechanisms in evolutionary cardiology failure. Ann N Y Acad Sci 2010; 1188: 58-67.

4. Ashrafian H, Frenneaux MP, Opie LH. Metabolic mechanisms in heart failure. Circulation 2007; 116:434-448.

5. Yan L, Wei X, Tang QZ, Feng J, Zhang Y, Liu C, et al. Cardiac-specific mindin overexpression attenuates cardiac hypertrophy via blocking AKT/GSK3beta and TGF-beta1-Smad signalling. Cardiovasc Res 2011; 92:85-94.

6. Frey N, Katus HA, Olson EN, Hill JA. Hypertrophy of the heart: a new therapeutic target?. Circulation 2004; 109:1580-1589.

7. Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med 1990; 322:1561-1566.

8. Satoh M, Ogita H, Takeshita K, Mukai Y, Kwiatkowski DJ, Liao JK. Requirement of Rac1 in the development of cardiac hypertrophy. Proc Natl Acad Sci USA 2006; 103:7432-7437.

9. Murtaza I, Wang HX, Mushtaq S, Javed Q, Li PF. Interplay of phosphorylated apoptosis repressor with CARD, casein kinase-2 and reactive oxygen species in regulating endothelin-1-Induced cardiomyocyte hypertrophy. Iran J Basic Med Sci 2013; 16:928-935.

10. Najafi M. Effects of postconditioning, preconditioning and perfusion of L-carnitine during whole period of ischemia/ Reperfusion on cardiac hemodynamic functions and myocardial infarction size in isolated rat heart. Iran J Basic Med Sci 2013; 16:640-647.

11. Olson EN, Schneider MD. Sizing up the heart: development redux in disease. Genes Dev 2003; 17:1937-1956.

12. Molkentin JD, Dorn Ⅱ GW. Cytoplasmic signaling pathways that regulate cardiac hypertrophy. Annu Rev Physiol 2001; 63:391-426.

13. Inanloo Rahatloo K, Davaran S, Elahi E. Lack of Association between the MEF2A Gene and Coronary Artery Disease in Iranian Families. Iran J Basic Med Sci 2013; 16:950-954.

14. Mehdizadeh R, Parizadeh MR, Khooei AR, Mehri S, Hosseinzadeh H. Cardioprotective effect of saffron extract and safranal in isoproterenol-induced myocardial infarction in wistar rats. Iran J Basic Med Sci 2013; 16:56-63.

15. Li R, Wu Y, Manso AM, Gu Y, Liao P, Israeli S, et al. beta1 integrin gene excision in the adult murine cardiac myocyte causes defective mechanical and signaling responses. Am J Pathol 2012; 180:952-962.

16. Rastegar T, Minaee MB, Habibi Roudkenar M, Raghardi Kashani I, Amidi F, Abolhasani F, et al. Improvement of expression of alpha6 and beta1 Integrins by the co-culture of adult mouse spermatogonial stem cells with SIM mouse embryonic fibroblast cells (STO) and growth factors. Iran J Basic Med Sci 2013; 16:134-139.

17. Langeggen H, Berge KE, Johnson E, Hetland G. Human umbilical vein endothelial cells express complement receptor 1 (CD35) and complement receptor 4 (CD11c/CD18) in vitro. Inflammation 2002; 26:103-110.

18. Vorup-Jensen T, Ostermeier C, Shimaoka M, Hommel U, Springer TA. Structure and allosteric regulation of the alpha X beta 2 integrin I domain. Proc Natl Acad Sci U S A 2003; 100:1873-1878.

19. Pham CG, Harpf AE, Keller RS, Vu HT, Shai SY, Loftus JC, et al. Striated muscle-specific beta(1D)-integrin and FAK are involved in cardiac myocyte hypertrophic response pathway. Am J Physiol Heart Circ Physiol 2000; 279:H2916-H2926.

20. Ross RS, Pham C, Shai SY, Goldhaber JI, Fenczik C, Glembotski CC, et al. Beta1 integrins participate in the hypertrophic response of rat ventricular myocytes. Circ Res 1998; 82:1160-1172.

21. Larjava H, Koivisto L, Heino J, Hakkinen L. Integrins in Periodontal Disease. Exp Cell Res 2014; 325:104-110.

22. Hynes RO. Integrins: bidirectional, allosteric signaling machines. Cell 2002; 110:673-687.

23. de Simone G, Devereux RB, Celentano A, Roman MJ. Left ventricular chamber and wall mechanics in the presence of concentric geometry. J Hypertens 1999; 17:1001-1006.

24. de Simone G, Greco R, Mureddu G, Romano C, Guida R, Celentano A, et al. Relation of left ventricular diastolic properties to systolic function in arterial hypertension. Circulation 2000; 101:152-157.

25. Grossman W, Paulus WJ. Myocardial stress and hypertrophy: a complex interface between biophysics and cardiac remodeling. J Clin Investig 2013; 123:3701-3703.

26. Kucukler N, Kurt IH, Topaloglu C, Gurbuz S, Yalcin F. The effect of valsartan on left ventricular myocardial functions in hypertensive patients with left ventricular hypertrophy. J Cardiovasc Med (Hagerstown) 2012; 13:181-186.

27. Hua Y, Zhang Y, Ren J. IGF-1 deficiency resists cardiac hypertrophy and myocardial contractile dysfunction: role of microRNA-1 and microRNA-133a. J Cell Mol Med 2012; 16:83-95.

28. Li YC, Liu YY, Hu BH, Chang X, Fan JY, Sun K, et al. Attenuating effect of post-treatment with QiShen YiQi Pills on myocardial fibrosis in rat cardiac hypertrophy. Clin Hemorheol Microcirc 2012; 51:177-191.

29. Schuster A, Ishida M, Morton G, Bigalke B, Moonim MT, Nagel E. Value of cardiovascular magnetic resonance imaging in myocardial hypertrophy. Clin Res cardiol 2012; 101:237-238.

30. Cines DB, Pollak ES, Buck CA, Loscalzo J, Zimmerman GA, McEver RP, et al. Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood 1998; 91:3527-3561.

31. Bouvard D, Brakebusch C, Gustafsson E, Aszodi A, Bengtsson T, Berna A, et al. Functional consequences of integrin gene mutations in mice. Circ Res 2001; 89:211-223.

32. Caiado F, Dias S. Endothelial progenitor cells and integrins: adhesive needs. Fibrogenesis Tissue Repair 2012; 5:4.

33. Leslie K, Blay R, Haisch C, Lodge A, Weller A, Huber S. Clinical and experimental aspects of viral myocarditis. Clin Microbiol Rev 1989; 2:191-203.

34. Johnston RK, Balasubramanian S, Kasiganesan H, Baicu CF, Zile MR, Kuppuswamy D. Beta3 integrin-mediated ubiquitination activates survival signaling during myocardial hypertrophy. FASEB J 2009; 23:2759-2771.

35. Suryakumar G, Kasiganesan H, Balasubramanian S, Kuppuswamy D. Lack of beta3 integrin signaling contributes to calpain-mediated myocardial cell loss in pressure-overloaded myocardium. J Cardiovas Pharmacol 2010; 55:567-573.

36. Blauwet LA, Cooper LT. Myocarditis. Prog Cardiovasc Dis 2010; 52:274-288.