Int J Sports Med 2007; 28(9): 749-755
DOI: 10.1055/s-2007-964899
Training & Testing

© Georg Thieme Verlag KG Stuttgart · New York

Increased Cx43 and Angiogenesis in Exercised Mouse Hearts

M. Bellafiore1 , 2 , G. Sivverini1 , D. Palumbo1 , F. Macaluso1 , A. Bianco1 , A. Palma2 , F. Farina1 , 2
  • 1Department of Experimental Medicine, University of Palermo, Palermo, Italy
  • 2Faculty of Motor Sciences, University of Palermo, Palermo, Italy
Further Information

Publication History

accepted after revision August 2, 2006

Publication Date:
23 April 2007 (online)

Abstract

Several studies focused on the macroscopic architecture of increased cardiac wall induced by exercise training. Our goal was to evaluate myocardiocyte, interstitial and vascular component, and connexin-43 expression in endurance-trained mouse hearts. Sixty-three 10-week-old male Swiss mice were divided into four sedentary groups (C0, C15, C30 and C45) and three groups exercised respectively for 15 (T15-D; running intensity [RI]: 3.18 m/min; running duration [RD]: 75 min/first week and 150 min/second week), 30 (T30-D; RI: 3.96 m/min; RD: 150 min/third week and 225 min/fourth week) and 45 days (T45-D; RI: 3.96 m/min and 4.8 m/min, respectively for the fifth and sixth week; RD: 300 min) on a treadmill. Morphometric analyses were performed to quantify myocardiocyte size and number, and the capillary and interstitial connective tissue (ICT) area. We assessed the expression of ventricle myosin light chain-II, vimentin and connexin-43 by western blot analyses. Our results showed a hypertrophy of the interventricular septum and left ventricle in T30-D and T45-D mice that was not due to variations in myofibrillar content, myocardiocyte size and number, or ICT quantity but to a significant increase in the capillary area. The microvascular remodeling was associated with vimentin increased expression in ICT cells and connexin-43 upregulation. The first phenomenon might be related to an enhanced request of remodeling and growth factors; the second suggests a new role of connexin-43 in cardiac angiogenesis.

References

  • 1 Beltrami A P, Barlucchi L, Torella D, Baker M, Limana F, Chimenti S, Kasahara H, Rota M, Musso E, Urbaneck K, Leri A, Kajstura J, Nadal-Ginard B, Anversa P. Adult cardiac stem cells are multipotent and support myocardial regeneration.  Cell. 2003;  114 763-776
  • 2 Bowles D K, Farra R P, Starnes J W. Exercise training improves cardiac function following ischemia in the isolated, working rat heart.  Am J Physiol. 1992;  263 H804-H809
  • 3 Brown M D. Exercise and coronary vascular remodeling in the healthy heart.  Exp Physiol. 2003;  88 645-658
  • 4 Child J S, Barnard R T, Taw R L. Cardiac hypertrophy and function in master endurance runners and sprinters.  J Appl Physiol. 1984;  57 176-181
  • 5 Fagard R H. Impact of different sports and training on cardiac structure and function.  Cardiol Clin. 1997;  15 397-412
  • 6 Formigli L, Ibba-Manneschi L, Perna A M, Pacini A, Polidori L, Nediani C, Modesti P A, Nosi D, Tani A, Celli A, Neri-Serneri G G, Quercioli F, Zecchi-Orlandini S. Altered Cx43 expression during myocardial adaptation to acute and chronic volume overloading.  Histol Histopathol. 2003;  18 359-369
  • 7 Hart G. Exercise-induced cardiac hypertrophy: a substrate for sudden death in athletes?.  Exp Physiol. 2003;  88 639-644
  • 8 Hudlicka O, Brown M D, Walter H, Weiss J B, Bate A. Factors involved in capillary growth in the heart.  Mol Cell Biochem. 1995;  147 57-68
  • 9 Hudlicka O, Brown M D. Postnatal growth of the heart and its blood vessels.  J Vasc Res. 1996;  33 266-287
  • 10 Iemitsu M, Maeda S, Miyauchi T, Matsuda M, Tanaka H. Gene expression profiling of exercise-induced cardiac hypertrophy in rats.  Acta Physiol Scand. 2005;  185 259-270
  • 11 Kanno S, Saffits J E. The role of myocardial gap junctions in electrical conduction and arrhythmogenesis.  Cardiovasc Pathol. 2001;  10 169-177
  • 12 Koyama T, Xie Z, Gao M, Suzuki J, Batra S. Adaptive changes in the capillary network in the left ventricle of rat heart.  Jpn J Physiol. 1998;  48 229-241
  • 13 Marino T A, Kent R L, Uboh C E, Fernandez E, Thompson E W, Cooper G. Structural analysis of pressure versus volume overload hypertrophy of cat right ventricle.  Am J Physiol. 1985;  249 H371-H379
  • 14 Maron B J. Structural features of the athlete heart as defined by echocardiography.  J Am Coll Cardiol. 1986;  7 190-203
  • 15 Mathew S, Mascareno E, Siddiqui M A. A ternary complex of transcription factors, Nished and NFATc4, and co-activator p 300 bound to an intronic sequence, intronic regulator element, is pivotal for the upregulation of myosin light chain-2v gene in cardiac hypertrophy.  J Biol Chem. 2004;  279 41018-41027
  • 16 Mel'nikova N P, Timoshin S S, Zhivotova E Y. Changes in DNA synthesis and morphometric indexes of the myocardium in albino rats treated with angiotensin II.  Bull Exp Biol Med. 2003;  135 247-259
  • 17 Peters N S, Green C R, Poole-Wilson P A, Severs N J. Reduced content of connexin43 gap junctions in ventricular myocardium from hypertrophied and ischemic human hearts.  Circulation. 1993;  88 864-875
  • 18 Saffitz J E, Kleber A G. Effects of mechanical forces and mediators of hypertrophy on remodeling of gap junctions in the heart.  Circ Res. 2004;  94 585-591
  • 19 Saffitz J E, Yamada K A. Do alterations in intercellular coupling play a role in cardiac contractile dysfunction?.  Circulation. 1998;  97 630-632
  • 20 Skalak T C, Price R J, Zeller P J. Where do new arterioles come from? Mechanical forces and microvessel adaptation.  Microcirculation. 1998;  5 91-100
  • 21 Swynghedauw B. Molecular mechanisms of myocardial remodeling.  Physiol Rev. 1999;  79 215-249
  • 22 Tomanek R J, Torry R J. Growth of the coronary vasculature in hypertrophy: mechanisms and model dependence.  Cell Mol Biol Res. 1994;  40 129-136
  • 23 Tomanek R J. Exercise-induced coronary angiogenesis.  Med Sci Sports Exerc. 1994;  26 1245-1251
  • 24 Urhausen A, Kindermann W. Sports-specific adaptations and differentiation of the athlete's heart.  Sports Med. 1999;  28 237-244
  • 25 Walker D L, Vacha S J, Kirby M L, Lo C W. Connexin43 deficiency causes dysregulation of coronary vasculogenesis.  Dev Biol. 2005;  284 479-498
  • 26 Weber K T, Brilla C G. Pathological hypertrophy and cardiac interstitium. Fibrosis and renin-angiotensin-aldosterone system.  Circulation. 1991;  83 1849-1865
  • 27 White F C, McKirnan D M, Breisch E A, Guth B D, Liu Y M, Bloor C M. Adaptation of the left ventricle to exercise-induced hypertrophy.  J Appl Physiol. 1987;  62 1097-1103
  • 28 White F C, Bloor C M. Coronary vascular remodeling and coronary resistance during chronic ischemia.  Am J Cardiovasc Pathol. 1992;  4 193-202
  • 29 White F C, Bloor C M, Mckirnan D M, Carrol S M. Exercise training in swine promotes growth of arteriolar bed and capillary angiogenesis in heart.  J Appl Physiol. 1998;  85 1160-1168
  • 30 Yamashita N, Baxter G F, Yellon D M. Exercise directly enhance myocardial tolerance to ischaemia-reperfusion injury in the rat through a protein kinase C mediated mechanism.  Heart. 2001;  85 331-336

molecular biologist Marianna Bellafiore

Department of Experimental Medicine, Human Anatomy Section
Faculty of Motor Sciences
University of Palermo

M. Toselli, 87 B

Palermo

Italy

Email: bellafiore@unipa.it

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