The collagen metabolism, disrupted endothelium, the endothelial progenitor cells and their microvesicles in acute rheumatic fever

BackgroundAcute rheumatic fever (ARF) and its chronic sequelae, rheumatic heart disease (RHD) contributes to valvular dysfunction and significant cardiovascular disability and endocardial damage is considered the primary pathophysiological mechanism underlying ARF. This study examined peripheral blood markers of endothelial injury and function in ARF and RHD patients and compared them to healthy controls. MethodIn this prospective observational study, the levels of collagen intermediates, matrix metalloproteinases, tissue inhibitors of matrix metalloproteinases, brain natriuretic peptide, Anti-DNaseB, VEGF, E-selectin, VCAM, and ICAM in circulation were estimated. The study also isolated hemangioblastic and monocytic endothelial progenitor cells and their respective microvesicles from the peripheral blood of patients and control samples. ResultsProcollagen type I carboxy-terminal propeptide, cross-linked c-telopeptide of type I, and procollagen III c-terminal propeptide levels were higher in RHD subjects compared to patients with ARF. The ARF patients had the highest levels of matrix metalloproteinases 10 (MMP-10) followed by chronic patients and healthy controls. The ratio of tissue inhibitors of matrix metalloproteinases TIMP-1 and MMP-10 was lowest in healthy controls. At the cellular level, there were higher number of monocytic endothelial progenitor cells (EPCs) in ARF subjects as compared to healthy controls. For hemangioblastic EPCs, there was no significant difference between chronic subjects and healthy controls, though their early subtype was higher in chronic subjects. The hemangioblastic EPCs microvesicles were more abundant in ARF compared to RHD patients. ConclusionThe greater number of EPCs and respective microvesicles confirm the continued disruption of the endothelium in ARF, and during the progression of the disease, the majority of EPCs undergo apoptosis. Obituary StatementThis study was conceived and designed by SR, PU, and Prof. Rajnish Juneja, Professor at AIIMS. Prof. Rajnish Juneja expired in April 2018 while the study was ongoing (1). Mr. Suran Nambisan, a research fellow at NII, was part of the team who initiated the experimental work. Dr. Suran Nambisan expired in January 2023. This paper is dedicated to both of them. It was the profound love for mankind and unwavering dedication to perfection by Prof. Rajnish Juneja that brought together a remarkable team to undertake this study. Dr. Suran Nambisan embarked on his professional research journey by successfully establishing and standardizing a few intricate protocols used in this study.