Mechanism Underlying Increased Cardiac Extracellular Matrix Deposition in Perinatal Nicotine Exposed Offspring.

Mechanism Underlying Increased Cardiac Extracellular Matrix Deposition in Perinatal Nicotine Exposed Offspring. Am J Physiol Heart Circ Physiol. 2020 Aug 14;: Authors: Chuang TD, Ansari A, Yu C, Sakurai R, Harb A, Liu J, Khorram O, Rehan VK Abstract Although increased predisposition to cardiac fibrosis and cardiac dysfunction has been demonstrated in the perinatally nicotine exposed heart, the underlying mechanisms remain unclear. Using a well-established rat model and cultured primary neonatal rat cardiac fibroblasts, the effect of perinatal nicotine exposure on offspring heart extracellular matrix deposition and the likely underlying mechanisms were investigated. Perinatal nicotine exposure resulted in increased collagen type I (COL1A1) and III (COL3A1) deposition along with a decrease in miR-29 family and an increase in long non-coding RNA myocardial infarction associated transcript (MIAT) levels in offspring heart. Nicotine treatment of isolated primary neonatal rat cardiac fibroblasts suggested that these effects were mediated via nicotinic acetylcholine receptors including α7 and the induced collagens accumulation was reversed by a gain-of function of miR-29 family. Knockdown of MIAT resulted in increased miR-29 family and decreased COL1A1 and COL3A1 levels, suggesting nicotine-mediated MIAT induction as the underlying mechanism for nicotine-induced collagen deposition. Luciferase reporter assay and RNA immunoprecipitation stu...
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Tags: Am J Physiol Heart Circ Physiol Source Type: research