Acute Exposure to Cigarette Smoking Followed by Myocardial Infarction Aggravates Renal Damage in an In Vivo Mouse Model

Abstract

Cigarette smoking (S) is a risk factor for progressive chronic kidney disease, renal dysfunction, and renal failure. In this study, the effect of smoking on kidney function was investigated in a mouse model of myocardial infarction (MI) using 4 groups: control (C), smoking (S), MI, and S+MI. Histological analysis of S+MI group showed alterations in kidney structure including swelling of the proximal convoluted tubules (PCTs), thinning of the epithelial lining, focal loss of the brush border of PCTs, and patchy glomerular retraction. Molecular analysis revealed that nephrin expression was significantly reduced in the S+MI group, whereas sodium-hydrogen exchanger-1 (NHE-1) was significantly increased, suggesting altered glomerular filtration and kidney functions. Moreover, S+MI group, but not S alone, showed a significant increase in the expression of connective tissue growth factor (CTGF) and fibrotic proteins fibronectin (FN) and α-smooth muscle actin (SMA), in comparison to controls, in addition to a significant increase in mRNA levels of IL-6 and TNF-α inflammatory markers. Finally, reactive oxygen species (ROS) production was significantly accentuated in S+MI group concomitant with a significant increase in NOX-4 protein levels. In conclusion, smoking aggravates murine acute renal damage caused by MI at the structural and molecular levels by exacerbating renal dysfunction.

Protocol for the Isolation and Super-resolution dSTORM Imaging of RyR2 in Cardiac Myocytes

“…Data presented in this section are summarized in Tables 1 and 2. In agreement with other groups and confirming our previous data [28,29,31], we observed a progressive LV remodeling over the course of 30 days after initiation of MI. LV remodeling was evidenced by consistently increasing LV volumes (R = 0.99, R 2 = 0.98, P<0.0012) and progressively deteriorating systolic function measured by EF ( Figure 2, R = −0.73, R 2 = 0.53, P<0.0001) and CO ( Figure 3).…”

“…All animal experiments and procedures were performed according to an experimental protocol approved by AUB Institutional Animal Care and Use Committee in compliance with the Guide for Care and Use of Laboratory Animals of the Institute for Laboratory Animal Research of the National Academy of Sciences, U.S.A. Mice were allocated into two groups: study group (n=9) and sham operated group (n=6). Sixteen months old C57BL/6J male mice weighing 30-35 g underwent left anterior descending (LAD) coronary artery ligation surgery as previously described [28,29]. The age of experimental animals was chosen to represent translational power of our study and to mimic the average age of 50-55 years of MI incidence in humans [30].…”

Tobacco cigarette smoking exacerbates aortic calcification in an early stage of myocardial infarction in a female mouse model

“…MI was induced by permanent ligation of the LAD coronary artery as described (A. Kaplan et al, ; Kobeissy et al, ). Occlusion of LAD was confirmed by the appearance of a pale color in the anterior wall of the left ventricle (LV) and sinus tachychardia elevation on the electrocardiogram using Indus Mouse Monitor system after ligation.…”

Cerebral blood flow alteration following acute myocardial infarction in mice

“…Sixteen months old C57BL/6J male mice weighing 30–35 g underwent left anterior descending (LAD) coronary artery ligation surgery as previously described [28,29]. The age of experimental animals was chosen to represent translational power of our study and to mimic the average age of 50–55 years of MI incidence in humans [30].…”