Abstract
Enhanced angiogenesis, or capillary growth, has a prominent role among the various beneficial effects of exercise training on the myocardium. The aim of the present study is to assess if training-induced increases in capillarity and vascularization persist after 4 weeks of detraining. Adult male rats were trained to run on a treadmill for 10 weeks at ∼60% VO2max, which did not induce cardiac hypertrophy, but increased (P < 0.05) the soleus/body weight ratio, left ventricle capillarity and von Willebrand-positive cell density (n = 6). In another group of animals (n = 6) subjected to training followed by 4-week detraining, the soleus/body weight ratio returned to normal, with only partial reversal of left ventricle capillarity and von Willebrand-positive cell density. Markers of angiogenesis (VEGF, KDR/VEGF-R2 and HIF-1α mRNA, studied by real-time RT-PCR) were upregulated at the end of training, and returned to baseline value after detraining. Electron microscopy highlighted some morphological features in trained hearts (endothelial cell sprouting and bridges and pericyte detachment), suggestive of endothelial cell proliferation and capillary growth that were absent in untrained and detrained hearts. We conclude that the training-induced increase in cardiac capillarity and vascularization are retained for some time upon cessation of the training program even in the absence of angiogenic stimuli.
Similar content being viewed by others
Abbreviations
- VEGF:
-
Vascular endothelial growth factor
- VEGF-R2:
-
Vascular endothelial growth factor receptor 2
- bFGF:
-
Basic fibroblast growth factor
- HIF-1:
-
Hypoxia-inducible factor-1
References
American Physiological Society (2006) Resource book for the design of animal exercise protocols, February 2006. http://www.the-aps.org/pa/action/exercise/book.pdf
Bergers G, Song S (2005) The role of pericytes in blood-vessel formation and maintenance. Neuro Oncol 7:452–464
Bloor CM (2005) Angiogenesis during exercise and training. Angiogenesis 8:263–271
Bronikowski AM, Carter PA, Morgan TJ, Garland T, Ung N, Pugh TD, Weindruch R, Prolla TA (2003) Lifelong voluntary exercise in the mouse prevents age-related alterations in gene expression in the heart. Physiol Genomics 12:128–138
Brown MD (2003) Exercise and coronary vascular remodelling in the healthy heart. Exp Physiol 88:645–658
Brown MD, Hudlicka O (2003) Modulation of physiological angiogenesis in skeletal muscle by mechanical forces: involvement of VEGF and metalloproteinases. Angiogenesis 6:1–14
Bruel A, Nyengaard JR (2005) Design-based stereological estimation of the total number of cardiac myocytes in histological sections. Basic Res Cardiol 100:311–319
Conway EM, Collen D, Carmeliet P (2001) Molecular mechanisms of blood vessel growth. Cardiovasc Res 49:507–521
Djonov V, Baum O, Burri PH (2003) Vascular remodeling by intussceptive angiogenesis. Cell Tissue Res 314:107–117
Efthimiadou A, Asimakopoulos B, Nikolettos N, Giatromanolaki A, Sivridis E, Lialiaris TS, Papachristou DN, Kontoleon E (2006) The angiogenetic effect of intramuscular administration of b-FGF and a-FGF on cardiac muscle: The influence of exercise on muscle angiogenesis. J Sports Sci 24:849–854
Falcieri E, Luchetti F, Burattini S, Canonico B, Santi S, Papa S (2000) Lineage-related sensitivity to apoptosis in human tumor cells undergoing hyperthermia. Histochem Cell Biol 113:135–144
Gigante B, Tarsitano M, Cimini V, De Falco S, Persico MG (2004) Placenta growth factor is not required for exercise-induced angiogenesis. Angiogenesis 7:277–284
Gustafsson T, Kraus WE (2001) Exercise-induced angiogenesis-related growth and transcription factors in skeletal muscle, and their modification in muscle pathology. Front Biosci 6:75–89
Hanson A (2007) How old is a rat in human years. Rat Behav Biol. http://www.ratbehavior.org/rats.html
Hearse DJ (1994) Myocardial ischaemia: can we agree on a definition for the 21st century? Cardiovasc Res 28:1737–144
Helisch A, Schaper S (2003) Arteriogenesis: the development and growth of collateral arteries. Microcirculation 10:83–97
Hudlicka O, Brown MD, Egginton S (1992) Angiogenesis in skeletal and cardiac muscle. Physiol Rev 72:369–417
Iemitsu M, Maeda S, Jesmin S, Otsuki T, Miyauchi T (2006) Exercise training improves aging-induced downregulation of VEGF angiogenic signaling cascade in hearts. Am J Physiol Heart Circ Physiol 291:H1290–H1298
Kemi OJ, Haram PM, Wisloff U, Ellingsen O (2004) Aerobic fitness is associated with cardiomyocyte contractile capacity and endothelial function in exercise training and detraining. Circulation 109:2897–904
Kutryk MJB, Stewart DJ (2003) Angiogenesis of the heart. Microsc Res Tech 60:138–158
Laughlin MH, Tomanek RJ (1987) Myocardial capillarity and maximal capillarity diffusion capacity in exercise-trained dogs. J Appl Physiol 63:1481–1486
Livak JK, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods 25:402–408
Ljungqvist A, Unge G (1973) The proliferative activity of the myocardial tissue in various form of experimental cardiac hypertrophy. Acta Pathol Microbiol Scand Sect A 81:233–240
Maeda S, Miyauchi T, Kakiyama T, Sugawara J, Iemitsu M, Irukayama-Tomobe Y, Murakami H, Kumagai Y, Kuno S, Matsuda M (2001) Effects of exercise training of 8 weeks and detraining on plasma levels of endothelium-derived factors, endothelin-1 and nitric oxide, in healthy young humans. Life Sci 69:1005–1016
Marini M, Lapalombella R, Margonato V, Ronchi R, Samaja M, Scapin C, Gorza L, Maraldi T, Carinci P, Ventura C, Veicsteinas A (2007) Mild exercise training, cardioprotection and stress gene profile. Eur J Appl Physiol 99:503–510
National Institutes of Health Physical activity and cardiovascular health (1995) NIH Consensus Development Conference Statement 13:11–22
Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucl Acids Res 29:e45
Powers SK, Quindry J, Hamilton K (2004) Aging, exercise, and cardioprotection. Ann N Y Acad Sci 1019:462–470
Prior BM, Yang HT, Terjung RL (2004) What makes vessels grow with exercise training? J Appl Physiol 97:1119–1128
Ruth EB (1935) Metamorphosis of the pubic symphysis. I. The white rat (Mus norvegicus albinus). Anat Rec 64:1–7
Schaper W, Ito W (1996) Molecular mechanisms of coronary collateral vessel growth. Circ Res 79:911–919
Ventura-Clapier R, Mettauer B, Bigard X (2007) Beneficial effects of endurance training on cardiac and skeletal muscle energy metabolism in heart failure. Cardiovasc Res 73:10–18
Wang H, Keiser JA (1998) Vascular endothelial growth factor upregulates the expression of matrix metalloproteinases in vascular smooth muscle: role of flt-1. Circ Res 83:832–840
Weibel ER, Hsia CCW, Ochs M (2007) How much is there really? Why stereology is essential in lung morphometry. J Appl Physiol 102:459–467
White FC, Bloor CM, McKirnan MD, Carroll SM (1998) Exercise training in swine promotes growth of arteriolar bed and capillary angiogenesis in heart. J Appl Physiol 85:1160–1168
Wisloff U, Helgerud J, Kemi OJ, Ellingsen O (2001) Intensity-controlled treadmill running in rats: VO(2 max) and cardiac hypertrophy. Am J Physiol Heart Circ Physiol 280:H1301–H1310
Yellon DM, Downey JM (2003) Preconditioning the myocardium: from cellular physiology to clinical cardiology. Physiol Rev 83:1113–1151
Yoon YS, Johnson IA, Park JS, Diaz L, Losordo DW (2004) Therapeutic myocardial angiogenesis with vascular endothelial growth factors. Mol Cell Biochem 264:63–74
Acknowledgments
This study was supported by grants from the Italian Ministry of University and Research (PRIN 2004054720) and from the Cariplo Foundation (2005 Project).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Marini, M., Falcieri, E., Margonato, V. et al. Partial persistence of exercise-induced myocardial angiogenesis following 4-week detraining in the rat. Histochem Cell Biol 129, 479–487 (2008). https://doi.org/10.1007/s00418-007-0373-8
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00418-007-0373-8