Background and aim of the study: Different patterns of fibroblast-mediated remodeling of the extracellular matrix (ECM) might be expected between patients with pressure- and volume-induced left ventricular hypertrophy.
Methods: Patients with chronic pressure-overload due to aortic stenosis (AS, n = 19) and chronic volume-overload due to either aortic regurgitation (AR, n = 9) or mitral regurgitation (MR, n = 10) were examined. The amount of interstitial collagen was quantified by using circular-polarization-microscopy in picrosirius red-stained biopsies. Biopsies from 10 patients with mild cardiomyopathy served as controls. In a subgroup, collagen type-I (Coll-I) and collagen type-III (Coll-III) gene expression was evaluated by quantitative RT-PCR. After immunohistological staining, procollagen-I/procollagen-III ratio and density of fibroblasts (FB) per vision-field were analyzed.
Results: The amount of interstitial cardiac fibrosis (ICF) was significantly higher in AS (5.7 +/- 4.1 g/m2), AR (8.8 +/- 4.9 g/m2) or MR (4.7 +/- 2.8 g/m2) than in controls (2.3 +/- 1.5 g/m2) (p = 0.003). The amount of thick collagen fibers was higher in AR than in AS, where-by density of fibroblasts did not differ. In volume-overloaded ventricles, the Coll-I/Coll-III ratio was shifted towards Coll-I, and in pressure-overloaded ventricles towards Coll-III. The severity of ECM remodeling was positively correlated with wall stress and impaired diastolic function, but not with systolic function or clinical symptoms.
Conclusion: Remodeling of the ECM is specific for left ventricular volume and pressure overload, and may serve as an early indicator for inadequate adaptation.