Collagen 18A1 /Endostatin Expression in the Progression of Right Ventricular Remodeling and Dysfunction in Pulmonary Arterial Hypertension.
Anjira S AmbadeMario NaranjoTijana TuhyRose YuMery MarimoutouAllen D EverettLarissa A ShimodaStefan L ZimmermanIlton M Cubero SalazarCatherine E SimpsonRyan J TedfordSteven HsuPaul M HassounRachel L DamicoPublished in: American journal of respiratory cell and molecular biology (2024)
Numerous studies have demonstrated that endostatin (ES), a potent angiostatic peptide derived from collagen type XVIII alpha 1 chain and encoded by COL18A1 , is elevated in pulmonary arterial hypertension (PAH). Importantly, elevated ES has consistently been associated with altered hemodynamics, poor functional status, and adverse outcomes in adult and pediatric PAH. This study used serum samples from patients with Group I PAH and plasma and tissue samples derived from the Sugen/Chronic hypoxic (SuHx) rat pulmonary hypertension (PH) model to define associations between COL18A1 /ES and disease development, including hemodynamics, right ventricular (RV) remodeling, and RV dysfunction. Using cardiac magnetic resonance (CMR) imaging and advanced hemodynamic assessments with pressure-volume (PV) loops in patients with PAH to assess RV-pulmonary arterial (PA) coupling, we observed a strong relationship between circulating ES levels and metrics of RV structure and function. Specifically, RV mass and the ventricular mass index (VMI) were positively associated with ES while RV ejection fraction and RV-PA coupling were inversely associated with ES levels. Our animal data demonstrates that the development of PH is associated with increased COL18A1 /ES in the heart as well as the lungs. Disease-associated increases in COL18A1 mRNA and protein were most pronounced in the RV compared to the left ventricle (LV) and lung. COL18A1 expression in the RV was strongly associated with disease-associated changes in RV mass, fibrosis, and myocardial capillary density. These findings indicate that COL18A1 /ES increase early in disease development in the RV and implicate COL18A1/ES in pathologic RV dysfunction in PAH.
Keyphrases
- mycobacterium tuberculosis
- pulmonary arterial hypertension
- pulmonary hypertension
- pulmonary artery
- magnetic resonance
- ejection fraction
- oxidative stress
- left ventricular
- magnetic resonance imaging
- polycyclic aromatic hydrocarbons
- squamous cell carcinoma
- radiation therapy
- young adults
- aortic stenosis
- transcatheter aortic valve replacement
- neoadjuvant chemotherapy
- electronic health record
- coronary artery disease
- tissue engineering
- aortic valve
- ionic liquid
- data analysis
- contrast enhanced