Mechanisms of Nicotine-dependent Activation of Cardiac Fibroblasts
Publication Date
July 2019
Location
LSU Health Medical Education Building
Document Type
Abstract
Start Date
26-7-2019 9:00 AM
End Date
26-7-2019 12:00 PM
Description
The rising popularity of electronic nicotine delivery systems (ENDS) has created concern over the physiological effects of inhaled e-liquid components, particularly nicotine. The increasing presence of tobacco companies in this market and access to open-system devices, which allow for individual customization of the e-liquid’s composition, add to the worry that ENDS use could be more dangerous than is advertised. Cigarette smoke has a multitude of detrimental effects, and inhaled nicotine alone may trigger similar responses. Of particular consideration is the effect of nicotine use on fibroblasts because of their role as producers of the extracellular matrix (ECM) proteins that provide stability and aid in the function of the surrounding tissue. Pulmonary fibroblasts undergo accelerated proliferation and increased ECM collagen production following exposure to nicotine. Likewise, cardiac fibroblasts show nicotine-dependent transdifferentiation into myocardiofibroblasts. Myocardiofibroblast activation is typically an acute process providing cardioprotection in response to cardiac stress or injury. Chronic activation, however, may accelerate progression of heart disease via an over-accumulation of ECM. We hypothesize that nicotine activates cardiac fibroblasts by binding to the alpha-7 nicotinic acetylcholine receptors (nAChR), leading to the disruption of compensatory mechanisms in favor of a more deleterious cellular response, which will result in excess ECM production, fibrosis, and increased susceptibility to cardiovascular disease. Fibroblasts extracted from cardiac tissue of naïve male rats are grown in vitro and exposed to nicotine for 12, 24, and 48 hours in the presence and absence of inhibitors of the renin-angiotensin system (RAS) – the signaling pathway believed to be responsible for increased ECM production. Following nicotine treatment, quantitative reverse transcription polymerase chain reaction (qPCR) measurements are utilized to monitor changes in the mRNA transcription of markers of myocardiofibroblast activation, including lysyl oxidase (LOX), alpha-smooth muscle actin (α-SMA), and collagen I and III. Wound healing and collagen gel contraction assays are used to obtain functional information about potential nicotine-dependent alterations in the cells. Ultimately, we plan to expand these experiments to include a mouse model of nicotine vapor exposure to closely mimic inhaled nicotine use. This research could provide new insight into physiological responses to nicotine consumption and a basis for tighter regulation on ENDS devices.
Recommended Citation
Vargas, Diego, "Mechanisms of Nicotine-dependent Activation of Cardiac Fibroblasts" (2019). Summer Research Internship Program. 3.
https://digitalscholar.lsuhsc.edu/srip/2019/postbac/3
Mechanisms of Nicotine-dependent Activation of Cardiac Fibroblasts
LSU Health Medical Education Building
The rising popularity of electronic nicotine delivery systems (ENDS) has created concern over the physiological effects of inhaled e-liquid components, particularly nicotine. The increasing presence of tobacco companies in this market and access to open-system devices, which allow for individual customization of the e-liquid’s composition, add to the worry that ENDS use could be more dangerous than is advertised. Cigarette smoke has a multitude of detrimental effects, and inhaled nicotine alone may trigger similar responses. Of particular consideration is the effect of nicotine use on fibroblasts because of their role as producers of the extracellular matrix (ECM) proteins that provide stability and aid in the function of the surrounding tissue. Pulmonary fibroblasts undergo accelerated proliferation and increased ECM collagen production following exposure to nicotine. Likewise, cardiac fibroblasts show nicotine-dependent transdifferentiation into myocardiofibroblasts. Myocardiofibroblast activation is typically an acute process providing cardioprotection in response to cardiac stress or injury. Chronic activation, however, may accelerate progression of heart disease via an over-accumulation of ECM. We hypothesize that nicotine activates cardiac fibroblasts by binding to the alpha-7 nicotinic acetylcholine receptors (nAChR), leading to the disruption of compensatory mechanisms in favor of a more deleterious cellular response, which will result in excess ECM production, fibrosis, and increased susceptibility to cardiovascular disease. Fibroblasts extracted from cardiac tissue of naïve male rats are grown in vitro and exposed to nicotine for 12, 24, and 48 hours in the presence and absence of inhibitors of the renin-angiotensin system (RAS) – the signaling pathway believed to be responsible for increased ECM production. Following nicotine treatment, quantitative reverse transcription polymerase chain reaction (qPCR) measurements are utilized to monitor changes in the mRNA transcription of markers of myocardiofibroblast activation, including lysyl oxidase (LOX), alpha-smooth muscle actin (α-SMA), and collagen I and III. Wound healing and collagen gel contraction assays are used to obtain functional information about potential nicotine-dependent alterations in the cells. Ultimately, we plan to expand these experiments to include a mouse model of nicotine vapor exposure to closely mimic inhaled nicotine use. This research could provide new insight into physiological responses to nicotine consumption and a basis for tighter regulation on ENDS devices.
Comments
Mentor: Jason Gardner, PhD, Department of Physiology