Endocardial Endothelial Dysfunction and Unknown Polymorphic Composite Accumulation in Heart Failure.

Hsuan-Fu Kuo,Feng-Yen Lin,Yu-Ru Liu,Tzu-Chieh Lin,Chia-Yang Li,Chien-Sung Tsai,Chong-Chao Hsieh,Chih-Hsin Hsu,Wei-Shiung Lian,Po-Len Liu,Tsung-Ying Lee,Chi-Yuan Huang,I-Fan Liu,Yung-Hsiang Chen

doi:10.3390/biomedicines9101465

Abstract

The accumulation of unknown polymorphic composites in the endocardium damages the endocardial endothelium (EE). However, the composition and role of unknown polymorphic composites in heart failure (HF) progression remain unclear. Here, we aimed to explore composite deposition during endocardium damage and HF progression. Adult male Sprague–Dawley rats were divided into two HF groups—angiotensin II-induced HF and left anterior descending artery ligation-induced HF. Heart tissues from patients who had undergone coronary artery bypass graft surgery (non-HF) and those with dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM) were collected. EE damage, polymorphic unknown composite accumulation, and elements in deposits were examined. HF progression reduced the expression of CD31 in the endocardium, impaired endocardial integrity, and exposed the myofibrils and mitochondria. The damaged endocardial surface showed the accumulation of unknown polymorphic composites. In the animal HF model, especially HF caused by myocardial infarction, the weight and atomic percentages of O, Na, and N in the deposited composites were significantly higher than those of the other groups. The deposited composites in the human HF heart section (DCM) had a significantly higher percentage of Na and S than the other groups, whereas the percentage of C and Na in the DCM and ICM groups was significantly higher than those of the control group. HF causes widespread EE dysfunction, and EndMT was accompanied by polymorphic composites of different shapes and elemental compositions, which further damage and deteriorate heart function.

Highlights

According to the American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for heart failure (HF), HF due to left ventricular dysfunction is categorized according to the left ventricular ejection fraction (LVEF) into HF with reduced ejection fraction (HFrEF; usually considered LVEF 40% or less) and HF with preserved ejection fraction (HFpEF) [1]
HF-Induced EE Injury Led to Myocardium Myofibril Fragmentation and Irrespective of whether it is hypertensive or ischemic HF, EE dysfunction initiates the progression of HF [28]
We found that the dilated cardiomyopathy (DCM) and ICM groups had apparent endocardial damage and were accompanied by the deposition of unknown composites on the EE (Figure 1B)

Summary

Introduction

According to the American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for heart failure (HF), HF due to left ventricular dysfunction is categorized according to the left ventricular ejection fraction (LVEF) into HF with reduced ejection fraction (HFrEF; usually considered LVEF 40% or less) and HF with preserved ejection fraction (HFpEF) [1]. Dysfunction of the endocardial endothelium (EE) leads to the progression of HF [2]. Endocardial dysfunction is associated with cardiovascular diseases [3]. Typical endocardial endothelial lesions have been implicated in inflammation, thrombosis, sepsis, atrial fibrillation, ischemia/reperfusion injury, myocardial infarction (MI), cardiac hypertrophy, and HF [2,4]. The EE is a critical source of cardiomyocytes, and it can periodically release nitric oxide into the subendocardial space. In HF, high concentrations of neurohormones induce oxidative stress and cause selective damage to the EE, reducing the mechanical performance and contractility of the adjacent cardiomyocytes. Partial damage or complete loss of EE can reduce cardiomyocyte contractility and affect cardiac contractile performance [7,8]

Objectives

Methods

Results

Conclusion