Abstract 14318: Collagen Cross-Linking but not Collagen Amount Associates with Elevated Filling Pressures in Heart Failure Patients of Hypertensive Origin. Potential Role of Lysyl Oxidase
We investigated whether the quality of myocardial collagen associates with elevated left-sided filling pressures (FPs) in 38 hypertensive patients with stage C chronic heart failure (HF). FPs were assessed invasively measuring pulmonary capillary wedge pressure (PCWP). Left ventricular chamber stiffness (KLV) was calculated from the deceleration time of the early mitral filling wave. The fraction of myocardial volume occupied by total collagen tissue (CVF) and collagen type I fibers (CIVF) was assessed histomorphologically. The degree of collagen cross-linking (CCL), which determines the formation of insoluble stiff collagen (insCol), 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 PCWP (≤12 mm Hg, n=16), patients with elevated PCWP (>12 mm Hg, n=22) exhibited increases of KLV, CVF, CIVF, CCL, insCol and LOX. PCWP was correlated with KLV (r=0.639, P<0.001), insCol (r=0.474, P<0.005), CCL (r=0.625, P<0.001) and LOX (r=0.410, P<0.05) in all patients, but not with CVF or CIVF. In addition, CCL was correlated with insCol (r=0.612, P<0.005), LOX (r=0.538, P<0.01), KLV (r=0.535, P<0.005), peak filling rate (r=-0.343, P<0.05), ejection fraction (r=-0.430, P<0.01) and NT-proBNP (r=0.421, P<0.05) in all patients. These associations were independent of confounding factors. These findings indicate that in hypertensive patients with stage C HF it is only the quality of collagen (i.e., degree of cross-linking) what associates with elevated FPs. It is suggested that LOX-mediated excessive collagen cross-linking facilitates the increase in LV stiffness with the resulting elevation of FPs in these patients.
- © 2012 by American Heart Association, Inc.