The accumulation
of lipids in cardiomyocytes contributes to cardiac
dysfunction. The specific blockage of cardiomyocyte cholesteryl ester
(CE) loading by antibodies (Abs) against the P3 sequence (Gly1127–Cys1140) of the LRP1 receptor improves
cardiac insulin sensitivity. The impact of anti-P3 Abs on high-fat
diet (HFD)-induced cardiac extracellular matrix (ECM) biophysical
alterations was analyzed. Both IrP (without Abs) and P3-immunized
rabbits (with Abs) were randomized into groups fed either HFD or a
standard chow diet. Cardiac lipids, proteins, and carbohydrates were
characterized by Fourier transform infrared spectroscopy in the attenuated
total reflectance mode. The hydric organization and physical structure
were determined by differential scanning calorimetry. HFD increased
the levels of esterified lipids, collagen, and α-helical structures
and upregulated fibrosis, bound water, and ECM plasticization in the
heart. The inhibitory effect of anti-P3 Abs on cardiac CE accumulation
was sufficient to reduce the collagen-filled extracellular space,
the level of fibrosis, and the amount of bound water but did not counteract
ECM plasticization in the heart of hypercholesterolemic rabbits.