Abstract 2798: Myocardial Titin Isoform Expression in Concentric and Eccentric Left Ventricular Remodeling
Titin lowers cardiac muscle stiffness through a shift in isoform expression from the stiff N2B isoform to the compliant N2BA isoform. In patients with eccentric LV remodeling due to dilated or ischemic cardiomyopathy, myocardial overexpression of the compliant N2BA isoform relates to LV dilatation. To explore the relation between myocardial titin isoform expression and LV geometry over a wider range of LV volume and mass, titin isoform expression was investigated not only in patients with eccentric LV remodeling and cardiomyopathy (CMP) but also in patients with concentric LV remodeling due to hypertension (HT) or aortic stenosis (AS). Titin isoform expression was determined in LV biopsies of controls (n=2) and of patients with CMP (n=3), HT (n5) or AS (n7). No patient had coronary artery disease. Expression of titin isoforms was analysed using gel electrophoresis and reported as a ratio of titin isoforms (N2BA/N2B). LV end diastolic volume index (LVEDVI) and LV mass index (LVMI) were derived from LV angiograms and 2D-echocardiograms. Over a wide range of LVEDVI (from 51 ml/m2 to 160 ml/m2) and over a wide range of LVMI (from 86 g/m2 to 212 g/m2), the N2BA/N2B ratio related to both LVEDVI (r=0.63; p<0.03) and to LVMI (r=0.83; p<0.001) (Figure⇓).
Conclusion: During concentric and eccentric LV remodeling, myocardial titin isoform expression relates both to LV volume and mass. At larger LV volume or mass, there is higher myocardial expression of the compliant N2BA titin isoform. Interspecies comparison of myocardial titin isoform expression reveals a similar trend because expression of the compliant N2BA titin isoform is also upregulated in larger mammals with larger LV volume and mass.