Identification of new biophysical markers for pathological ventricular remodelling in tachycardia‐induced dilated cardiomyopathy

Abstract

Our aim was to identify biophysical biomarkers of ventricular remodelling in tachycardia‐induced dilated cardiomyopathy (DCM). Our study includes healthy controls (N = 7) and DCM pigs (N = 10). Molecular analysis showed global myocardial metabolic abnormalities, some of them related to myocardial hibernation in failing hearts, supporting the translationality of our model to study cardiac remodelling in dilated cardiomyopathy. Histological analysis showed unorganized and agglomerated collagen accumulation in the dilated ventricles and a higher percentage of fibrosis in the right (RV) than in the left (LV) ventricle (P = .016). The Fourier Transform Infrared Spectroscopy (FTIR) 1st and 2nd indicators, which are markers of the myofiber/collagen ratio, were reduced in dilated hearts, with the 1st indicator reduced by 45% and 53% in the RV and LV, respectively, and the 2nd indicator reduced by 25% in the RV. The 3rd FTIR indicator, a marker of the carbohydrate/lipid ratio, was up‐regulated in the right and left dilated ventricles but to a greater extent in the RV (2.60‐fold vs 1.61‐fold, P = .049). Differential scanning calorimetry (DSC) showed a depression of the freezable water melting point in DCM ventricles – indicating structural changes in the tissue architecture – and lower protein stability. Our results suggest that the 1st, 2nd and 3rd FTIR indicators are useful markers of cardiac remodelling. Moreover, the 2nd and 3rd FITR indicators, which are altered to a greater extent in the right ventricle, are associated with greater fibrosis.

Biophysical and Lipidomic Biomarkers of Cardiac Remodeling Post-Myocardial Infarction in Humans

“…The spectral signatures of the structural proteins of ECM and the myofibers in the human heart are similar to those previously reported in murine [ 4 ] and porcine hearts [ 5 ]. One of the most significant alterations observed in the FTIR spectra of human LV INF vs. LV or RV was a strong increase in the 1338 cm −1 band, which has been shown to be specific to collagen [ 6 , 25 , 36 ].…”

“…These TAG species were C53:2 ( p = 0.041), C54:1 ( p = 0.036), and C54:2 ( p = 0.033). The decrease in TAG in human LV compared to RV was previously reported in a porcine model [ 5 ] and likely reflects a higher effort and more energetic consumption of LV. Most of the cholesterol was found in the form of free cholesterol (FC, 2.03%) ( Figure S7B ), with a minor proportion found as cholesteryl esters (CE, 0.90%) ( Figure S7C ).…”

“…To compare the spectral signature of the human heart with previous data collected from animal hearts [ 4 , 5 ], the average FTIR spectra of mice, pig, and human right ventricles were superimposed ( Figure 1 ). Table S2 summarizes the different FTIR absorption bands detected in human compared to pig and mice right ventricles, as well as their assignments, according to previously published data in transmission or ATR mode [ 5 , 6 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ]. The major absorption bands in these spectra were the amide A, the amide I, and the amide II, which are mainly associated with proteins in freeze-dried tissues.…”

“…Table S3 shows a comparison of the IR bands between RVs, LVs and LV INFs of the human hearts compiled from IR spectra. Specific assignments of these bands were performed according to the literature [ 5 , 6 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ]. Most of the IR bands previously described in murine and porcine cardiac control tissues are also present in the RV, LV, and LV INF of human hearts.…”

“…Detailed information about the chemical composition and physical structure of infarct zones post-MI remains limited. Previous studies from our group have shown that Fourier transform infrared (FTIR) spectroscopy has the potential to highlight the main alterations that occur in cardiac remodeling in a post-MI mice model [ 4 ], as well as in a pig model of tachycardia-induced dilated cardiomyopathy [ 5 ]. The FTIR spectra of freeze-dried mice’s left ventricles showed amides I and II to be the major absorptions bands.…”