title: Collagen XV is necessary for modeling of the extracellular matrix and its deficiency predisposes to cardiomyopathy.
abstract: BACKGROUND
  The extracellular matrix (ECM) is a major determinant of the structural integrity and functional properties of the myocardium in common pathological conditions, and changes in vasculature contribute to cardiac dysfunction. Collagen (Col) XV is preferentially expressed in the ECM of cardiac muscle and microvessels.
  
  
  OBJECTIVE
  We aimed to characterize the ECM, cardiovascular function and responses to elevated cardiovascular load in mice lacking Col XV (Col15a1(-/-)) to define its functional role in the vasculature and in age- and hypertension-associated myocardial remodeling.
  
  
  RESULTS
  Cardiac structure and vasculature were analyzed by light and electron microscopy. Cardiac function, intraarterial blood pressure, microhemodynamics, and gene expression profiles were studied using echocardiography, telemetry, intravital microscopy, and PCR, respectively. Experimental hypertension was induced with angiotensin II or with a nitric oxide synthesis inhibitor. Under basal conditions, lack of Col XV resulted in increased permeability and impaired microvascular hemodynamics, distinct early-onset and age-dependent defects in heart structure and function, a poorly organized fibrillar collagen matrix with marked interstitial deposition of nonfibrillar protein aggregates, increased tissue stiffness, and irregularly organized cardiomyocytes. In response to experimental hypertension, Col15a1 gene expression was increased in the left ventricle of wild-type mice, and mRNA expression of natriuretic peptides (ANP and BNP) and ECM modeling were abnormal in Col15a1(-/-) mice.
  
  
  CONCLUSIONS
  Col XV is necessary for ECM organization in the heart, and for the structure and functions of microvessels. Col XV deficiency leads to a complex cardiac phenotype and predisposes the subject to pathological responses under cardiac stress.
authors.affiliation: Oulu Center for Cell-Matrix Research, Biocenter Oulu, University of Oulu, Finland.
authors.forename: Karolina
authors.initials: K
authors.lastname: Rasi
authors.forename: Jarkko
authors.initials: J
authors.lastname: Piuhola
authors.forename: Marcus
authors.initials: M
authors.lastname: Czabanka
authors.forename: Raija
authors.initials: R
authors.lastname: Sormunen
authors.forename: Mika
authors.initials: M
authors.lastname: Ilves
authors.forename: Hanna
authors.initials: H
authors.lastname: Leskinen
authors.forename: Jaana
authors.initials: J
authors.lastname: Rysä
authors.forename: Risto
authors.initials: R
authors.lastname: Kerkelä
authors.forename: Paul
authors.initials: P
authors.lastname: Janmey
authors.forename: Ritva
authors.initials: R
authors.lastname: Heljasvaara
authors.forename: Keijo
authors.initials: K
authors.lastname: Peuhkurinen
authors.forename: Olli
authors.initials: O
authors.lastname: Vuolteenaho
authors.forename: Heikki
authors.initials: H
authors.lastname: Ruskoaho
authors.forename: Peter
authors.initials: P
authors.lastname: Vajkoczy
authors.forename: Taina
authors.initials: T
authors.lastname: Pihlajaniemi
authors.forename: Lauri
authors.initials: L
authors.lastname: Eklund
mesh_terms: D000367:Age Factors; D000375:Aging; D000804:Angiotensin II; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics; D009202:Cardiomyopathies / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D003094:Collagen / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D003326:Coronary Circulation; D004195:Disease Models, Animal; D004452:Echocardiography; D004548:Elasticity; D004791:Enzyme Inhibitors; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D005838:Genotype; D006352:Heart Ventricles / Q000378:metabolism / Q000503:physiopathology; D006439:Hemodynamics; D006973:Hypertension / Q000139:chemically induced / Q000150:complications* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008833:Microcirculation; D008854:Microscopy, Electron; D018715:Microscopy, Video; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D019331:NG-Nitroarginine Methyl Ester; D020097:Natriuretic Peptide, Brain / Q000235:genetics; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D013686:Telemetry; D020257:Ventricular Remodeling
chemical_list: D004791:Enzyme Inhibitors; D012333:RNA, Messenger; C553732:collagen XV, mouse; D000804:Angiotensin II; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D003094:Collagen; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester