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Collagen Cross-Linking But Not Collagen Amount Associates With Elevated Filling Pressures in Hypertensive Patients With Stage C Heart Failure: Potential Role of Lysyl Oxidase.
MedLine Citation:
PMID:  22824984     Owner:  NLM     Status:  Publisher    
We investigated whether the quality of myocardial collagen associates with elevated left-sided filling pressures in 38 hypertensive patients with stage C chronic heart failure. Filling pressures were assessed invasively measuring pulmonary capillary wedge pressure. Left ventricular chamber stiffness constant was calculated from the deceleration time of the early mitral filling wave. The fraction of myocardial volume occupied by total collagen tissue and collagen type I fibers was assessed histomorphologically. The degree of collagen cross-linking (CCL), which determines the formation of insoluble stiff collagen, was assessed by colorimetric and enzymatic procedures. The expression of lysyl oxidase (LOX), which regulates CCL, was assessed by Western blot. Compared with patients with normal pulmonary capillary wedge pressure (≤12 mm Hg; n=16), patients with elevated pulmonary capillary wedge pressure (>12 mm Hg; n=22) exhibited increases of left ventricular chamber stiffness constant, fraction of myocardial volume occupied by total collagen tissue, fraction of myocardial volume occupied by collagen type I fibers, CCL, insoluble stiff collagen, and LOX. Pulmonary capillary wedge pressure was correlated with left ventricular chamber stiffness constant (r=0.639; P<0.001), insoluble stiff collagen (r=0.474; P<0.005), CCL (r=0.625; P<0.001), and LOX (r=0.410; P<0.05) in all of the patients but not with fraction of myocardial volume occupied by total collagen tissue or fraction of myocardial volume occupied by collagen type I fibers. In addition, CCL was correlated with insoluble stiff collagen (r=0.612; P<0.005), LOX (r=0.538; P<0.01), left ventricular chamber stiffness constant (r=0.535; P<0.005), peak filling rate (r=-0.343; P<0.05), ejection fraction (r=-0.430; P<0.01), and amino-terminal propeptide of brain natriuretic peptide (r=0.421; P<0.05) in all of the patients. These associations were independent of confounding factors. These findings indicate that, in hypertensive patients with stage C heart failure, it is only the quality of collagen (ie, degree of cross-linking) that associates with elevated filling pressures. It is suggested that LOX-mediated excessive CCL facilitates the increase in left ventricular stiffness with the resulting elevation of filling pressures in these patients.
Begoña López; Ramón Querejeta; Arantxa González; Mariano Larman; Javier Díez
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-23
Journal Detail:
Title:  Hypertension     Volume:  -     ISSN:  1524-4563     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Division of Cardiovascular Sciences, Centre for Applied Medical Research, and Department of Cardiology and Cardiac Surgery, University of Navarra Clinic, University of Navarra, Pamplona, Spain; Division of Cardiology, Donostia University Hospital, San Sebastián, Spain.
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