Abstract 3585: Relative Expression of Fibronectin and Collagen I mRNAs is Related to Left Ventricular Diastolic Dimension in Myocardial Biopsies From Patients With Either Aortic Regurgitation or Aortic Stenosis
Background: Aortic regurgitation (AR) and aortic stenosis (AS) each cause cardiac hypertrophy characterized by changes in myocyte and extracellular matrix (ECM) biology. Experimental models of aortic outflow obstruction show abnormal myocardial collagen I (COLI) expression, whereas in our experimental model of aortic regurgitation, fibronectin (FN) expression was abnormal but COLI was unaffected. However, parallel data from humans with aortic valvular diseases are largely unavailable
Method: Tru-cut biopsies were obtained at the thickest portion of the LV free wall from patients with normal LV performance (ejection fraction >55%) undergoing aortic valve replacement (AVR) for isolated, pure AS (n=9) or isolated, pure AR (n=10), and from “control” pts with coronary artery disease (CAD) but no infarction undergoing elective bypass grafting (CABG) (n=7). RNA prepared with Qiagen kits was used to synthesize labeled cRNA to probe Affymetrix microarrays (Human Genome U133 Plus 2.0). All patients underwent pre-AVR echocardiography and catheterization.
Results: Concentrations of mRNAs encoding extracellular matrix proteins were highly correlated with one another, but showed no significant differences between diagnoses. Although, both COL1 and fibronectin mRNA concentrations correlated positively with LV diastolic dimension (DD) (COLI: r=0.61 for both AR and AS; FN: r=0.33 AR, r=0.37 AS), the regression lines for either COLI or fibronectin mRNA and LVDD for AR were shifted to the right of the line for AS. Moreover, the ratio of FN:COLI mRNAs was negatively correlated with LVDD (r=−0.63, p=0.008).
Conclusion: These observations suggest that, consistent with our experimental findings, alteration of ECM components is associated with LV dilatation; disordering of ECM proteins may be centrally involved in permitting progressive LV chamber dilatation, an important part of the pathophysiology of LV dysfunction and heart failure in AR.