Skip to main content
SpringerLink
Log in

Aging of myocardial collagen

  • Published:
Biogerontology Aims and scope Submit manuscript

Abstract

The objective of this article was to present a review of the collagen tissue of the heart muscle as a function of age. The myocardial collagen matrix consists of a network of fibrillar collagen which is intimately connected to the myocyte. Most collagen fibers reside in parallel with myocytes. These fibers may have a wavy, taut or coiled appearance. Fibrillar collagen types I and III are the major components of the myocardial collagen matrix. Collagen type I has been found to represent nearly 80% of the total collagen protein, while type III collagen is present in lower proportions (approximately 11%). Cardiac fibroblasts are the cellular source of fibrillar collagen, cardiac myocytes expressing only mRNA for type IV collagen. Collagens types I and III exhibit a high tensile strength which plays an important role in the behavior of the ventricle during the cardiac cycle. The collagen concentration and the intermolecular cross-linking of collagen increase with age. Measurements of collagen content in myocardial tissue siggest that it is the type I collagen fibers that increase in number and thickness in the aged. At the same time, electron microscopic observations have shown an increase in the number of collagen fibrils with a large diameter in the aging heart. The mechanism responsible for the myocardial fibrosis in the senescent myocardium is unclear. The collagen deposition in the myocardium could be due to the regulation of collagen byosinthesis at pre-translational levels. It is possible that the regulatory elements involved in this process are growth factors such as TGF-β1 and hormones and neurotransmitters. Details of regulatory mechanism that may come into play during aging may be elucidated by further investigations. The accumulation of collagen within the myocardium increases muscle stiffness. Myocardial function is affected by this process; this is usually reflected by incomplete relaxation during early diastolic filling, and presumably account for the decrease in early left ventricular diastolic compliance.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Ahumada GE and Saffitz JE (1984) Fibronectin in rat heart: a link between cardiac myocytes and collagen. J Histochem Cytochem 32: 383-388

    PubMed  CAS  Google Scholar 

  • Akamatsu FE, de Souza RR and Liberti EA (1999) Fall in the number of intracardiac neurons in aging rats. Mech Ageing Dev 190: 153-161

    Article  Google Scholar 

  • Annoni G, Luvar G, Arosio B, Gagliano N, Fiordaliso L, Latini R, Vergani C and Masson S (1998) Age-dependent expression of fibrosis-related genes and collagen deposition in rat myocardium. Mech Ageing Dev 101(1-2): 57-72

    Article  PubMed  CAS  Google Scholar 

  • Asif M., Egan J, Vasan S, Jyothirmayi GN, Masmekas MR, Lopes S, Williams C, Torres RL, Wagle D, Ulrich P, Cerami A, Brines M and Regan TJ (2000) An advanced glycation endproduct cross-link breaks can reverse age-related increases in myocardial stiffness. Proc Natl Acad Sci USA 97(6): 2809-2813

    Article  PubMed  CAS  Google Scholar 

  • Bashey RI, Torii S and Angrist A (1967) Age-related collagen and elastin content of human heart valve. J Gerontol 22: 203-208

    PubMed  CAS  Google Scholar 

  • Bonnin CM, Sparrow MP and Taylor RR (1978) Collagen synthesis and content turnover in cardiac and skeletal muscles of the adult fowl and changes during stretch-induced growth. Biochem J 176: 419-429

    Google Scholar 

  • Borg TK and Caulfied JB (1981) The collagen matrix of the heart. Fed Proc 40: 2037-2041

    PubMed  CAS  Google Scholar 

  • Brooks WV and Conrad CH (2000) Myocardial fibrosis in transforming growth factor ? (1) heterozygous mice. J Mol Cell Cardiol 32(2): 187-195

    Article  PubMed  CAS  Google Scholar 

  • Brilla CG, Maisch B, Zhwo G and Weber KT (1993) Reninangiotensin system and myocardial collagen matrix remodeling studies on collagen matrix regulation. Clin Invet 71: 35-41

    Google Scholar 

  • Burgess ML, Mccrea JC and Hedrick HL (2001) Age-associated changes in cardiac matrix and integrins. Mech Ageing Dev 122: 1939-1756

    Article  Google Scholar 

  • Burton AC (1954) Relation of structure to function of the tissues of the wall of the blood vessels. Physiol Rev 34: 619-624

    PubMed  CAS  Google Scholar 

  • Carvalho Filho E, Ferraz de Carvalho CA and de Souza RR (1996) Age-related changes in elastic fibers of human heart. Gerontology 42: 211-217

    PubMed  Google Scholar 

  • Caulfied JB and Borg TK (1979) The collagen network of the heart. Lab Invest 40: 364-372

    Google Scholar 

  • Caulfied JB and Wolkowicz PE (1988) Inducible collagenolytic activity in isolated perfused rat hearts. Am J Pathol 131: 199-215

    Google Scholar 

  • Caulfied JB and Wolkowicz PE (1990) Mechanism for cardiac dilatation. Heart Failure 6: 138-150

    Google Scholar 

  • Chakraborty A and Eghbali M (1989) Collagenase activity in the normal rat myocardium. A immunohistochemical method. Histochemistry 92: 391-398

    Article  PubMed  CAS  Google Scholar 

  • Chin JR, Murphy G and Werb Z (1985) Stromelysin, a connectivetissue degrading metalloendopeptidase secreted be stimulated rabbit synovial fibroblasts in parallel with collagenase. Biosynthesis, isolation characterization and substrates. J Biol Chem 260: 12367-12371

    PubMed  CAS  Google Scholar 

  • Clausen B (1963) Influence of age on chondroitin sulfates and collagen of human aorta, myocardium and skin. Lab Invest 12: 538-542

    PubMed  CAS  Google Scholar 

  • Constatine VS and Mowry RW (1968) Selective staining of human dermal collagen. II. The use of Picrosirius red FBA with polarization microscopy. J Invest Dermatol 50: 419-423

    Google Scholar 

  • Contard F, Koteliansky V, Marotte F, Dubud T, Rappaport L and Samuel J (1991) Specific alteration in the distribution of extracellular matrix components within rat myocardium during the development of pressure overload. Lab Invest 64: 65-75

    PubMed  CAS  Google Scholar 

  • Corman B, Duriez M, Poitevin P, Hendes D, Bruneval P, Tedgui A and Levy BI (1998) Amminoguanidine prevents age-related arterial stiffening and cardiac hypertrophy. Proc Natl Acad Sci USA 95(3): 1301-1306

    Article  PubMed  CAS  Google Scholar 

  • Debessa CRG, Maifrino LBM and de Souza RR (2001) Age related changes of collagen network of the human heart. Mech Ageing Dev 122: 1049-1058

    Article  Google Scholar 

  • Doering CW, Jalil JE and Janicki JS (1988) Collagen network remodeling and diastolic stiffness of the rat left ventricle with pressure overload hypertrophy. Cardiovasc Res 22: 686-695

    PubMed  CAS  Google Scholar 

  • Dogrell SA (2001) ALT-711 decreases cardiovascular stiffness and has potential in diabetes, hypertension and heart failure. Expert Opin Invest Drugs 10(5): 981-983

    Article  Google Scholar 

  • Dolber PC and Spach MS (1993) Conventional and confocal fluorescence microscopy of collagen fibers in the heart. J Histochem Cytochem 41: 465-469

    PubMed  CAS  Google Scholar 

  • Emery JL and Omens JH (1997) Mechanical regulation of myocardial growth during volume-overload hypertrophy in the rat. Am J Physiol 273: H1198-H1204

    PubMed  CAS  Google Scholar 

  • Eghbali M (1990) Collagen gene expression and molecular basis of fibrosis in the myocardium. Heart Failure 6: 125-128

    Google Scholar 

  • Eghbali M, Czaka MJ, Zeydel M, Weiner FR, Zern MA and Blumenfeld OO (1988) Collagen chain mRNAs in isolated heart cells from young and adult rats. J Mol Cell Cardiol 20: 267-276

    Article  PubMed  CAS  Google Scholar 

  • Eghbali M, Blumenfeld OO and Seifter S (1989) Localization of the fibers I, III and IV collagen mRNAs in rat heart cells by in situ hybridization. J Mol Cell Cardiol 21: 103-113

    Article  PubMed  CAS  Google Scholar 

  • Fleg JL (1986) Alterations in cardiovascular structure and function with advancing age. Am J Cardiol 57: 33c-44c

    Article  PubMed  CAS  Google Scholar 

  • Flint MH, Lyons MF, Meaney ME and Williams DE (1975) The Masson staining of collagen-an explanation of an apparent paradox. Histochem J 7: 529-546

    Article  CAS  Google Scholar 

  • Frank JS and Langer GA (1974) The myocardial interstitium: its structure and its role in ionic exchange. J Cell Biol 60: 586-601

    Article  PubMed  CAS  Google Scholar 

  • Ginetys E, Cloos PA, Borel O, Grimaud L, Delmas PD and Garnero P (2000) Racemization and isomerization of type I collagen Ctelopeptides in human bone and soft tissues: assessment of tissue turnover. Biochem J 345 pt 3: 481-485

    Article  Google Scholar 

  • Gomes OA, de Souza RR and Liberti EA (1997) A preliminary investigation of the effects of aging on the nerve cell number in the myenteric ganglia of human colon. Gerontology 43: 210-217

    PubMed  CAS  Google Scholar 

  • Grover-McKay M, Scholtz TD, Burns TL and Skorton DJ (1991) Myocardial collagen concentration and nuclear magnetic resonance relaxation times in the spontaneously hypertensive rat. Invest Radiol 26: 227-232

    PubMed  CAS  Google Scholar 

  • Hoyt RH, Collins SM and Skorton DJ (1984) Computer-assisted quantitation of myocardial fibrosis in histologic sections. Arch Pathol Lab Med 108: 280-283

    PubMed  CAS  Google Scholar 

  • Hoyt RH, Collins SM, Skorton DJ, Erickensen EE and Conyers D (1985) Assessment of fibrosis in infarcted human hearts by analysis of ultrasonic backscatter. Circulation 71: 740-744

    PubMed  CAS  Google Scholar 

  • Ignotz RA and Massague J (1986) Transform growth factor-? stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix. J Biol Chem 261: 4337-4345

    PubMed  CAS  Google Scholar 

  • Ito A and Nagase H (1988) Evidence that human rheumatoid synovial matrix metalloproteinase 3 is an endogenous activator of procollagenase. Arch Biochem Biophys 267: 211-219

    Article  PubMed  CAS  Google Scholar 

  • Jalil JE, Doering CW and Janicki JS (1989) Fibrillar collagen and myocardial stiffness in the intact hypertrophied rat ventricle. Circ Res 64: 1041-1046

    PubMed  CAS  Google Scholar 

  • Janicki JS (1992) Myocardial collagen remodeling and left ventricular diastolic function. Brazilian J Med Biol Res 25: 975-982

    CAS  Google Scholar 

  • Junqueira LCU, Cossermelli W and Brentani RR (1978) Differential staining of collagen type I, II and III by Sirius Red and polarization microscopy. Arch Histol Jpn 41: 267-274

    PubMed  CAS  Google Scholar 

  • Junqueira LCU, Bignolas G and Brentani RR (1979) Picrosirius staining plus polarization microscopy, a specific method for collagen detection in tissue sections. Histochem J 11: 447-455

    Article  PubMed  CAS  Google Scholar 

  • Leigh LC (1975) Changes in the ultrastructure of cardiac muscle in steers deprived of cooper. Res Vet Sci 18: 282-289

    PubMed  CAS  Google Scholar 

  • Masson S, Arosio B, Fiordalino F, Gagliano N, Calvillo L, Santanbrogio D, D'aquila S, Vergani C, Latini R and Annoni G (2000) Left ventricular response to beta adrenergic stimulation in aging rats. J Gerontol A Biol Sci Med Sci 55(1): 1335-1341

    Google Scholar 

  • Medugorac I (1980) Collagen content in different areas of normal and hypertrophied rat myocardium. Cardiovasc Res 14: 551-557

    PubMed  CAS  Google Scholar 

  • Medugorac I and Jacob R (1983) Characterization of left ventricular collagen in the rat. Cardiovasc Res 17: 15-21

    Article  PubMed  CAS  Google Scholar 

  • Montes GS and Junqueira LCU (1982) Biology of collagen. Rev Can Biol Expériment 41: 143-156

    CAS  Google Scholar 

  • Montes GS, Kristán RM, Shigihara KM, Tokoro R, Mourão PAS and Junqueira LCU (1980) Histochemical and morphological characterization of reticular fibers. Histochemistry 65: 131-141

    Article  PubMed  CAS  Google Scholar 

  • Morales MA, Ferdeghini EM, Piacenti M, Dattolo P, Distante A and Maggliore Q (2000) Age dependency of myocardial structure: a quantitative two-dimensional echocardiographic study in a normal population. Echocardiography 17: 201-208

    PubMed  CAS  Google Scholar 

  • Morita T, Shimada T, Kitamura H and Nakamura M (1991) Demonstration of connective tissue sheaths surrounding working myocardial cells and Purkinje cells of the sheep moderator band. Arch Hist Cytol 54: 539-550

    CAS  Google Scholar 

  • Nguyen CT, Hall CS, Scott MJ, Zhu Q, Marsh J and Wickline SA (2001) Age related alterations in cardiac structure and material properties in Fischer 344 rats. Ultrasound Med Biol 27: 611-619

    Article  PubMed  CAS  Google Scholar 

  • Olivetti G, Melissari M, Capasso JM and Anversa P (1991) Cardiomyopathy of aging human heart. Myocyte loss and reactive cellular hypertrophy. Circ Res 68: 1560-1568

    PubMed  CAS  Google Scholar 

  • Pardo A, Soto H, Monfort I and Perez-Tamayo R (1980) Collagenbound collagenase. Connect Tissue Res 7: 253-261

    PubMed  CAS  Google Scholar 

  • Perez-Tamayo R (1978) Pathology of collagen degradation. Am J Pathol 92: 509-566

    Google Scholar 

  • Robert V, Besse S, Sabri A, Silvestre JS, Assayag P, Nguyen VT, Swynghedauw B and Delcayre C (1997) Differential regulation of matrix metalloproteinase associated with aging and hypertension in the rat heart. Lab Invest 76(5): 729-738

    PubMed  CAS  Google Scholar 

  • Robinson TF, Cohen-Gould L and Factor SM (1983) The skeletal framework of mammalian heart muscle: arrangement of interand pericellular connective tissue structures. Lab Invest 49: 482-487

    PubMed  CAS  Google Scholar 

  • Robinson TF, Factor SM and Sonnenblick EH (1986) The heart as a suction pump. Sci Am 254: 84-91

    Article  PubMed  CAS  Google Scholar 

  • Robinson TF, Factor SM, Capasso JM, Wittenberg BA and Blumenfeld OO (1987) Morphology, composition and function of struts between cardiac myocytes of rat and hamster. Cell Tissue Res 249: 247-255

    Article  PubMed  CAS  Google Scholar 

  • Rossi P, Karsently G and Robert AB (1988) A nuclear factor 1 binding sites mediates transcriptional activation of a type I collagen promoter by transforming growth factor-?. Cell 52: 405-410

    Article  PubMed  CAS  Google Scholar 

  • Rosen SF and Bertozzi C (1994) The selectins and their ligands. Curr Opin Cell Biol 6: 663-6673

    Article  PubMed  CAS  Google Scholar 

  • Safar M (1990) Ageing and its effects on the cardiovascular system. Drugs 39 (Suppl 1): 1-8

    Article  PubMed  Google Scholar 

  • Sakai T and Gross J (1967) Some properties of the products of reaction of tadpole collagenase with collagen. Biochemistry 6: 518-524

    Article  PubMed  CAS  Google Scholar 

  • Sellars A and Reynolds JJ (1977) Identification and partial characterization of an inhibitor of collagenase from rabbit bone. Biochem J 139: 359-368

    Google Scholar 

  • Seltzer JL, Adams AS, Grant GA and Eisen AZ (1981) Purification and properties of a gelatin-specific neutral protease from human skin. J Biol Chem 256: 4662-4669

    PubMed  CAS  Google Scholar 

  • Sobel H and Marmorston J (1956) The possible role of gel-fibre ratio of connective tissue in the aging process. J Gerontol 11: 1-7

    Google Scholar 

  • Springman EB, Angleton EL, Birkedal-Hansen H and Van Hart HE (1990) Multiple mode of activation of latent human fibroblast collagenase: evidence for the role of a Cys73 active-site zinc complex in latency and a ‘cysteine switch’ mechanism for activation. Proc Natl Acad Sci (USA) 87: 364-376

    Article  CAS  Google Scholar 

  • Stricklin GP, Bauer EA, Jeffrey JJ and Aizen AZ (1977) Human skin collagenase: isolation of precursor and active forms from both fibroblasts and oral cultures. Biochemistry 16: 1607-1612

    Article  PubMed  CAS  Google Scholar 

  • Thomas DP, Zimmerman SD, Hansen TR, Martin DT and McCormick RJ (2000) Collagen gene expression in rat left ventricle: interactive effect of age and exercise training. J Appl Physiol 89: 1462-1468

    PubMed  CAS  Google Scholar 

  • Vaitkevicius PV, Lane M, Spurgeon H, Ingram DK, Roth GS, Egan JJ, Vasan S, Wagle DK, Ulrich P, Brines M, Werth JP, Carami A and Lakatta EG (2001) A cross-link breaker has sustained effects on arterial and ventricular properties in older rhesus monkeys. Proc Natl Acad Sci USA 98(30): 1171-1175

    Article  PubMed  CAS  Google Scholar 

  • Verzár F (1956) Das Altern des Collagens. Helv Physiol Pharmacol Acta 14: 207-221

    PubMed  Google Scholar 

  • Walsh RA (1987) Cardiovascular effects of ageing process. Am J Med 82 (Suppl 1B): 34-40

    Article  PubMed  CAS  Google Scholar 

  • Weber KT (1989) Cardiac interstitium in health and disease: the fibrillar collagen network. J Am Coll Cardiol 13: 1637-1652

    Article  PubMed  CAS  Google Scholar 

  • Weber KT, Clark WA, Janicki JS and Shroff SG (1987) Physiologic versus pathologic hypertrophy and pressure-overloaded. J Cardiovasc Pharmacol 10 (Suppl 6): S37-49

    PubMed  Google Scholar 

  • Weber KT, Janicki JS, Shroff SG, Pick R, Chen RM and Basley RT (1988) Collagen remodeling of the pressure overloaded hypertrophied non human primate myocardium. Circ Res 67: 757-765

    Google Scholar 

  • Weber KT, Brilla CG and Janicki JS (1990) Structural remodeling of myocardial collagen in systemic hypertension: function consequences and potencial therapy. Heart Failure 6: 129-137

    Google Scholar 

  • Welgus HG, Jeffrey JJ and Eisen AZ (1985) Human skin fibroblast collagenase: Interaction with substrate and inhibitor. Coll Relat Res 5: 167-175

    PubMed  CAS  Google Scholar 

  • Werb Z, Burleigh MC, Barret AJ and Starkey PM (1974) The interaction of alpha-2-macroglobulin with proteinases. Binding and inhibition of mammalian collagenase and other metal proteinases. Biochem J 139: 359-367

    PubMed  CAS  Google Scholar 

  • Whittaker P, Kloner RA, Boughner DR and Pickering JG (1994) Quantitative assessment of myocardial collagen with picrosirius red staining and circularly polarized light. Basic Res Cardiol 879: 397-410

    Article  Google Scholar 

  • Yang CM, Kandaswamy V, Young D and Sem S (1997) Changes in collagen phenotypes during progression and regression of cardiac hypertrophy. Cardiol Res 36(2): 236-246

    CAS  Google Scholar 

  • Zhang X, Azhar G, Chai J, Aheridan P, Nagano K, Brown T, Yang J, Khrapko K, Borras AM, Luwitts J, Misra RP and Wei JY (2001) Cardiomyopathy in transgenic mice cardiac-specific overexpression of serum response factor. Am J Physiol Heart Circ Physiol 280(4): H1782-1792

    PubMed  CAS  Google Scholar 

  • Zwolinski RJ, Hamlin CR And Kohn RR (1976) Age-related alterations in human heart collagen. Proc Soc Biol Med 152: 362-365

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo and Department of Anatomy, Unicid University Av. Cons Rodrigues Alves, 539/141, CEP 04014-011, São Paulo, Brazil

    R.R. de Souza

Authors
  1. R.R. de Souza
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

de Souza, R. Aging of myocardial collagen. Biogerontology 3, 325–335 (2002). https://doi.org/10.1023/A:1021312027486

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1021312027486

Search

Navigation