Remodeling of the cardiac extracellular matrix differs between volume- and pressure-overloaded ventricles and is specific for each heart valve lesion.

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.