Expression Profiles of α1nAChR, ERK1/2, c-FOS and Matrix Metalloproteinases Among Male Smokers with Acute Coronary
Nazirah Samah1, Faridah Mohd Nor2, Wan Mohammad Hafiz Wan Razali2,3
1Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, Kuala Lumpur 56000, Malaysia.
Insights
Smoking elevates key biomarkers linked to cardiovascular disease progression. This study reveals smoking-associated increases in alpha1nAChR, ERK, and MMP-9 in patients with coronary artery disease, impacting plaque stability and ACS risk.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Atherosclerosis Research
Background:
- Smoking is a primary risk factor for Acute Coronary Syndrome (ACS), a severe form of Coronary Artery Disease (CAD).
- Smoking's role in plaque instability is partly attributed to increased matrix metalloproteinase (MMP) activity, but molecular mechanisms are unclear.
- Understanding smoking's impact on specific molecular pathways in ACS is crucial for targeted interventions.
Purpose of the Study:
- To investigate the expression of alpha-1 nicotinic acetylcholine receptor (α1nAChR), ERK1/2, and c-FOS genes in CAD patients.
- To quantify matrix metalloproteinase (MMP) protein levels in relation to smoking status within atherosclerotic plaques and peripheral blood mononuclear cells (PBMCs).
- To elucidate smoking-associated molecular alterations in ACS pathogenesis.
Main Methods:
- Analysis of α1nAChR, ERK1/2, and c-FOS gene expression using RT-qPCR in plaque tissues and PBMCs.
- Measurement of MMP-2, MMP-9, and TIMP-3 protein levels via ELISA.
- Comparison of biomarker expression between smokers and non-smokers across ACS, chronic coronary syndrome (CCS), and control groups.
Main Results:
- Elevated ERK1/2 and c-FOS gene expression in plaque tissues of smokers versus non-smokers.
- Increased α1nAChR expression in PBMCs of chronic coronary syndrome smokers and ERK1/2 in ACS smokers.
- Significantly higher MMP-9 protein levels in both ACS and CCS patients compared to controls.
Conclusions:
- Smoking in CAD patients is associated with heightened expression of α1nAChR, ERK, and MMP-9.
- These findings suggest smoking induces alterations in the α1nAChR-ERK signaling pathway.
- Smoking-related changes in these biomarkers may contribute to plaque instability and ACS development.
Abstract:
Acute Coronary Syndrome (ACS) is a severe manifestation of Coronary Artery Disease (CAD) caused by the rupture of unstable atherosclerotic plaques, resulting in reduced myocardial blood flow. Smoking is a major risk factor for ACS and has been associated with increased matrix metalloproteinase (MMP) activity, which contributes to the degradation of the plaque fibrous cap. However, the molecular alterations associated with smoking in ACS remain incompletely understood. This study aimed to investigate the expression of α1nAChR, ERK1/2, and c-FOS genes, together with MMP protein levels in atherosclerotic plaque tissues and peripheral blood mononuclear cells (PBMCs) of CAD patients. A total of 41 atherosclerotic plaque samples (26 smokers, 15 non-smokers) and 180 clinical subjects [n = 30 per group: ACS, chronic coronary syndrome (CCS), and controls; smokers and non-smokers] were included. Gene expression of ⍺1nAChR, ERK 1/2, and c-FOS was analyzed by RT-qPCR, while protein levels of MMP-2, MMP-9, and TIMP 3 were measured using ELISA. The expression of ERK 1/2 and c-FOS were significantly higher in plaque tissues of smokers compared with non-smokers (1.671- and 1.327-fold; p < 0.05). In PBMCs, α1nAChR expression was higher in CCS smokers (1.383-fold), while ERK 1/2 expression was higher in ACS smokers (1.355-fold). MMP-9 levels were significantly elevated in ACS and CCS compared with controls (p < 0.001). In conclusion, smoking CAD patients demonstrated increased expression of α1nAChR, ERK and MMP-9, indicating smoking-associated alterations in ⍺1nAChR-ERK signaling-related biomarkers in ACS.
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