Abstract

The pathophysiology of heart failure with preserved ejection fraction (HFpEF) is a matter of investigation and its diagnosis remains challenging. Although the mechanisms that are responsible for the development of HFpEF are not fully understood, it is well known that nearly 80% of patients with HFpEF have concomitant hypertension. We investigated whether early biochemical alterations were detectable during HFpEF progression in salt-induced hypertensive rats, using Fourier-transformed infrared (FTIR) and Raman spectroscopic techniques as a new diagnostic approach. Greater protein content and, specifically, greater collagen deposition were observed in the left atrium and right ventricle of hypertensive rats, together with altered metabolism of myocytes. Additionally, Raman spectra indicated a conformational change, or different degree of phosphorylation/methylation, in tyrosine-rich proteins. A correlation was found between tyrosine content and cardiac fibrosis of both right and left ventricles. Microcalcifications were detected in the left and right atria of control animals, with a progressive augmentation from six to 22 weeks. A further increase occurred in the left ventricle and right atrium of 22-week salt-fed animals, and a positive correlation was shown between the mineral deposits and the cardiac size of the left ventricle. Overall, FTIR and Raman techniques proved to be sensitive to early biochemical changes in HFpEF and preceded clinical humoral and imaging markers.

Highlights

  • The pathophysiology of heart failure with preserved ejection fraction (HFpEF) is a matter of investigation and its diagnosis remains challenging

  • The amide III band showed an intense minimum at 1237 ­cm−1; at these wavenumbers, the major contribution came from c­ollagen[11]

  • All Raman spectra were normalized to the 1450 ­cm−1 band, which is mainly related to the lipid concentration in the tissue (Fig. 1b)

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Summary

Introduction

The pathophysiology of heart failure with preserved ejection fraction (HFpEF) is a matter of investigation and its diagnosis remains challenging. Half the patients with HF have normal contractility This medical condition of HF with preserved ejection fraction (HFpEF) is characterized by cardiac hypertrophy and increased stiffness of the heart, which compromise ventricular relaxation and reduce stroke v­ olume[2,3]. Metabolic diseases such as obesity, diabetes and hypertension often contribute to the development of ­HFpEF4. We further hypothesized that, during evolution toward HFpEF, due to the different stresses that occur in the four cardiac chambers, the biochemical modifications of the atria would be different from those of the ventricles To test these hypotheses, we investigated the progression of diastolic dysfunction and cardiac hypertrophy through application of the spectroscopic techniques to a rat model of salt-induced hypertension

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