Smad3 signaling promotes fibrosis while preserving cardiac and aortic geometry in obese diabetic mice

Circulation: Heart Failure

Volumn 8, Issue 4, 2015, Pages 788-798

  Biernacka, Anna ^a   Cavalera, Michele ^a   Wang, Junhong ^a   Russo, Ilaria ^a   Shinde, Arti ^a   Kong, Ping ^a   Gonzalez Quesada, Carlos ^a,b   Rai, Vikrant ^a   Dobaczewski, Marcin ^a,b   Lee, Dong Wook ^a   Wang, Xiao Fan ^c   Frangogiannis, Nikolaos G ^a,b  

^a ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

^b BAYLOR COLLEGE OF MEDICINE   (United States)

^c DUKE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Diabetes mellitus; Diabetic cardiomyopathies; Fibrosis; Obesity; TGF

Indexed keywords

COLLAGEN; LEPTIN; MATRIX METALLOPROTEINASE; SMAD3 PROTEIN; SMAD3 PROTEIN, MOUSE; TRANSFORMING GROWTH FACTOR BETA;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; ASCENDING AORTA; BLOOD VESSEL WALL; CONTROLLED STUDY; DIABETES MELLITUS; DIASTOLIC DYSFUNCTION; DISEASE ASSOCIATION; ENZYME ACTIVITY; FEMALE; GEOMETRY; HAPLOINSUFFICIENCY; HEART LEFT VENTRICLE; HEART MUSCLE COMPLIANCE; HEART MUSCLE FIBROSIS; HEART VENTRICLE HYPERTROPHY; HYPERTENSION; INSULIN RESISTANCE; MALE; MORTALITY; MOUSE; NITROSATIVE STRESS; NONHUMAN; OBESITY; OXIDATIVE STRESS; PATHOGENESIS; PRIORITY JOURNAL; ULTRASOUND; WEIGHT GAIN; ANIMAL; AORTA; AORTIC ANEURYSM; AORTIC RUPTURE; C57BL MOUSE; CARDIOMEGALY; COMPLICATION; DEFICIENCY; DIABETIC CARDIOMYOPATHIES; DISEASE MODEL; FIBROSIS; GENETICS; HEART LEFT VENTRICLE FUNCTION; HEART MUSCLE; HEART VENTRICLE REMODELING; KNOCKOUT MOUSE; LESIONS AND DEFECTS; METABOLISM; PATHOLOGY; PATHOPHYSIOLOGY; SIGNAL TRANSDUCTION; TIME; VASCULAR REMODELING;

ANIMALS; AORTA; AORTIC ANEURYSM; AORTIC RUPTURE; CARDIOMEGALY; DIABETIC CARDIOMYOPATHIES; DILATATION, PATHOLOGIC; DISEASE MODELS, ANIMAL; FEMALE; FIBROSIS; MALE; MATRIX METALLOPROTEINASES; MICE, INBRED C57BL; MICE, KNOCKOUT; MYOCARDIUM; OBESITY; SIGNAL TRANSDUCTION; SMAD3 PROTEIN; TIME FACTORS; TRANSFORMING GROWTH FACTOR BETA; VASCULAR REMODELING; VENTRICULAR DYSFUNCTION, LEFT; VENTRICULAR REMODELING;

EID: 84942936191     PISSN: 19413289     EISSN: 19413297     Source Type: Journal    
DOI: 10.1161/CIRCHEARTFAILURE.114.001963     Document Type: Article

References (34)

1. Marwick TH. Diabetic heart disease. Heart. 2006;92:296-300. doi: 10.1136/hrt.2005.067231.
2. Abel ED, Litwin SE, Sweeney G. Cardiac remodeling in obesity. Physiol Rev. 2008;88:389-419. doi: 10.1152/physrev.00017.2007.
3. Ho JE, Lyass A, Lee DS, Vasan RS, Kannel WB, Larson MG, Levy D. Predictors of new-onset heart failure: differences in preserved versus reduced ejection fraction. Circ Heart Fail. 2013;6:279-286. doi: 10.1161/CIRCHEARTFAILURE.112.972828.
4. Rubler S, Dlugash J, Yuceoglu YZ, Kumral T, Branwood AW, Grishman A. New type of cardiomyopathy associated with diabetic glomerulosclerosis. Am J Cardiol. 1972;30:595-602.
5. Asbun J, Villarreal FJ. The pathogenesis of myocardial fibrosis in the setting of diabetic cardiomyopathy. J Am Coll Cardiol. 2006;47:693-700. doi: 10.1016/j.jacc.2005.09.050.
6. Biernacka A, Dobaczewski M, Frangogiannis NG. TGF-β signaling in fibrosis. Growth Factors. 2011;29:196-202. doi: 10.3109/08977194.2011.595714.
7. Bujak M, Ren G, Kweon HJ, Dobaczewski M, Reddy A, Taffet G, Wang XF, Frangogiannis NG. Essential role of Smad3 in infarct healing and in the pathogenesis of cardiac remodeling. Circulation. 2007;116:2127-2138. doi: 10.1161/CIRCULATIONAHA.107.704197.
8. Flanders KC. Smad3 as a mediator of the fibrotic response. Int J Exp Pathol. 2004;85:47-64. doi: 10.1111/j.0959-9673.2004.00377.x.
9. Dobaczewski M, Bujak M, Li N, Gonzalez-Quesada C, Mendoza LH, Wang XF, Frangogiannis NG. Smad3 signaling critically regulates fibroblast phenotype and function in healing myocardial infarction. Circ Res. 2010;107:418-428. doi: 10.1161/CIRCRESAHA.109.216101.
10. Bhattacharyya S, Chen SJ, Wu M, Warner-Blankenship M, Ning H, Lakos G, Mori Y, Chang E, Nihijima C, Takehara K, Feghali-Bostwick C, Varga J. Smad-independent transforming growth factor-beta regulation of early growth response-1 and sustained expression in fibrosis: implications for scleroderma. Am J Pathol. 2008;173:1085-1099. doi: 10.2353/ajpath.2008.080382.
11. Wang S, Wilkes MC, Leof EB, Hirschberg R. Imatinib mesylate blocks a non-Smad TGF-beta pathway and reduces renal fibrogenesis in vivo. FASEB J. 2005;19:1-11. doi: 10.1096/fj.04-2370com.
12. Huntgeburth M, Tiemann K, Shahverdyan R, Schlóter KD, Schreckenberg R, Gross ML, Modersheim S, Caglayan E, Móller-Ehmsen J, Ghanem A, Vantler M, Zimmermann WH, Bohm M, Rosenkranz S. Transforming growth factorβ oppositely regulates the hypertrophic and contractile response to β-adrenergic stimulation in the heart. PLoS One. 2011;6:e26628. doi: 10.1371/journal.pone.0026628.
13. Westermann D, Rutschow S, Jger S, Linderer A, Anker S, Riad A, Unger T, Schultheiss HP, Pauschinger M, Tschpe C. Contributions of inflammation and cardiac matrix metalloproteinase activity to cardiac failure in diabetic cardiomyopathy: the role of angiotensin type 1 receptor antagonism. Diabetes. 2007;56:641-646. doi: 10.2337/db06-1163.
14. Lenski M, Kazakov A, Marx N, Bhm M, Laufs U. Effects of DPP-4 inhibition on cardiac metabolism and function in mice. J Mol Cell Cardiol. 2011;51:906-918. doi: 10.1016/j.yjmcc.2011.08.001.
15. Riehle C, Wende AR, Zaha VG, Pires KM, Wayment B, Olsen C, Bugger H, Buchanan J, Wang X, Moreira AB, Doenst T, Medina-Gomez G, Litwin SE, Lelliott CJ, Vidal-Puig A, Abel ED. PGC-1β deficiency accelerates the transition to heart failure in pressure overload hypertrophy. Circ Res. 2011;109:783-793. doi: 10.1161/CIRCRESAHA.111.243964.
16. Wu L, Derynck R. Essential role of TGF-beta signaling in glucoseinduced cell hypertrophy. Dev Cell. 2009;17:35-48. doi: 10.1016/j. devcel.2009.05.010.
17. Talior-Volodarsky I, Connelly KA, Arora PD, Gullberg D, McCulloch CA. α11 integrin stimulates myofibroblast differentiation in diabetic cardiomyopathy. Cardiovasc Res. 2012;96:265-275. doi: 10.1093/cvr/cvs259.
18. Wang HT, Liu CF, Tsai TH, Chen YL, Chang HW, Tsai CY, Leu S, Zhen YY, Chai HT, Chung SY, Chua S, Yen CH, Yip HK. Effect of obesity reduction on preservation of heart function and attenuation of left ventricular remodeling, oxidative stress and inflammation in obese mice. J Transl Med. 2012;10:145. doi: 10.1186/1479-5876-10-145.
19. Uusitupa MI, Mustonen JN, Airaksinen KE. Diabetic heart muscle disease. Ann Med. 1990;22:377-386.
20. Mandavia CH, Aroor AR, Demarco VG, Sowers JR. Molecular and metabolic mechanisms of cardiac dysfunction in diabetes. Life Sci. 2013;92:601-608. doi: 10.1016/j.lfs.2012.10.028.
21. Koitabashi N, Danner T, Zaiman AL, Pinto YM, Rowell J, Mankowski J, Zhang D, Nakamura T, Takimoto E, Kass DA. Pivotal role of cardiomyocyte TGF-β signaling in the murine pathological response to sustained pressure overload. J Clin Invest. 2011;121:2301-2312. doi: 10.1172/JCI44824.
22. Cavalera M, Wang J, Frangogiannis NG. Obesity, metabolic dysfunction, and cardiac fibrosis: pathophysiological pathways, molecular mechanisms, and therapeutic opportunities. Transl Res. 2014;S1931-5244(14)00164-9.
23. Ilkun O, Boudina S. Cardiac dysfunction and oxidative stress in the metabolic syndrome: an update on antioxidant therapies. Curr Pharm Des. 2013;19:4806-4817.
24. Bakin AV, Stourman NV, Sekhar KR, Rinehart C, Yan X, Meredith MJ, Arteaga CL, Freeman ML. Smad3-ATF3 signaling mediates TGF-beta suppression of genes encoding Phase II detoxifying proteins. Free Radic Biol Med. 2005;38:375-387. doi: 10.1016/j. freeradbiomed.2004.10.033.
25. Black D, Lyman S, Qian T, Lemasters JJ, Rippe RA, Nitta T, Kim JS, Behrns KE. Transforming growth factor beta mediates hepatocyte apoptosis through Smad3 generation of reactive oxygen species. Biochimie. 2007;89:1464-1473. doi: 10.1016/j.biochi.2007.09.001.
26. Michaeloudes C, Sukkar MB, Khorasani NM, Bhavsar PK, Chung KF. TGF-β regulates Nox4, MnSOD and catalase expression, and IL-6 release in airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 2011;300:L295-L304. doi: 10.1152/ajplung.00134.2010.
27. Neptune ER, Frischmeyer PA, Arking DE, Myers L, Bunton TE, Gayraud B, Ramirez F, Sakai LY, Dietz HC. Dysregulation of TGF-beta activation contributes to pathogenesis in Marfan syndrome. Nat Genet. 2003;33:407-411. doi: 10.1038/ng1116.
28. Gillis E, Van Laer L, Loeys BL. Genetics of thoracic aortic aneurysm: at the crossroad of transforming growth factor-β signaling and vascular smooth muscle cell contractility. Circ Res. 2013;113:327-340. doi: 10.1161/CIRCRESAHA.113.300675.
29. Wang Y, Ait-Oufella H, Herbin O, Bonnin P, Ramkhelawon B, Taleb S, Huang J, Offenstadt G, Combadire C, Rnia L, Johnson JL, Tharaux PL, Tedgui A, Mallat Z. TGF-beta activity protects against inflammatory aortic aneurysm progression and complications in angiotensin II-infused mice. J Clin Invest. 2010;120:422-432. doi: 10.1172/JCI38136.
30. Lindsay ME, Schepers D, Bolar NA, Doyle JJ, Gallo E, Fert-Bober J, Kempers MJ, Fishman EK, Chen Y, Myers L, Bjeda D, Oswald G, Elias AF, Levy HP, Anderlid BM, Yang MH, Bongers EM, Timmermans J, Braverman AC, Canham N, Mortier GR, Brunner HG, Byers PH, Van Eyk J, Van Laer L, Dietz HC, Loeys BL. Loss-of-function mutations in TGFB2 cause a syndromic presentation of thoracic aortic aneurysm. Nat Genet. 2012;44:922-927. doi: 10.1038/ng.2349.
31. Regalado ES, Guo DC, Villamizar C, Avidan N, Gilchrist D, McGillivray B, Clarke L, Bernier F, Santos-Cortez RL, Leal SM, Bertoli-Avella AM, Shendure J, Rieder MJ, Nickerson DA, Milewicz DM; NHLBI GO Exome Sequencing Project. Exome sequencing identifies SMAD3 mutations as a cause of familial thoracic aortic aneurysm and dissection with intracranial and other arterial aneurysms. Circ Res. 2011;109:680-686. doi: 10.1161/CIRCRESAHA.111.248161.
32. van de Laar IM, Oldenburg RA, Pals G, Roos-Hesselink JW, de Graaf BM, Verhagen JM, Hoedemaekers YM, Willemsen R, Severijnen LA, Venselaar H, Vriend G, Pattynama PM, Collee M, Majoor-Krakauer D, Poldermans D, Frohn-Mulder IM, Micha D, Timmermans J, Hilhorst-Hofstee Y, Bierma-Zeinstra SM, Willems PJ, Kros JM, Oei EH, Oostra BA, Wessels MW, Bertoli-Avella AM. Mutations in SMAD3 cause a syndromic form of aortic aneurysms and dissections with earlyonset osteoarthritis. Nat Genet. 2011;43:121-6.
33. van der Linde D, van de Laar IM, Bertoli-Avella AM, Oldenburg RA, Bekkers JA, Mattace-Raso FU, van den Meiracker AH, Moelker A, van Kooten F, Frohn-Mulder IM, Timmermans J, Moltzer E, Cobben JM, van Laer L, Loeys B, De Backer J, Coucke PJ, De Paepe A, Hilhorst-Hofstee Y, Wessels MW, Roos-Hesselink JW. Aggressive cardiovascular phenotype of aneurysms-osteoarthritis syndrome caused by pathogenic SMAD3 variants. J Am Coll Cardiol. 2012;60:397-403. doi: 10.1016/j. jacc.2011.12.052.
34. Tan CK, Tan EH, Luo B, Huang CL, Loo JS, Choong C, Tan NS. SMAD3 deficiency promotes inflammatory aortic aneurysms in angiotensin IIinfused mice via activation of iNOS. J Am Heart Assoc. 2013;2:e000269. doi: 10.1161/JAHA.113.000269.