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A Modified Two Kidney One Clip Mouse Model of Renin Regulation in Renal Artery Stenosis
Published on: October 26, 2020
Abrogation of lectin-like oxidized LDL receptor-1 attenuates acute myocardial ischemia-induced renal dysfunction by
Jingjun Lu1, Xianwei Wang, Wenze Wang
1Department of Emergency Medicine, Renmin Hospital of Wuhan University, Wuhan, China. lvjingjun@gmail.com
Abstract:
It is assumed that acute myocardial infarction affects renal function. To study the mechanism, we used mice following permanent ligation of their left coronary artery that results in extensive myocardial infarction. Soon after ligation, there was a marked rise in circulating pro-inflammatory cytokines and malondialdehyde (thiobarbituric acid-positive evidence of lipid peroxidation). Renal function had significantly declined by the third day in association with mild fibrosis, and swelling of glomeruli and tubules. There was a significant increase in the expression of the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), interelukin-1β, vascular cell adhesion molecule-1, and thiobarbituric acid-reactive substances in the kidney. Renal function showed some recovery by Day 21; however, there was progressive fibrosis of the kidneys. LOX-1 knockout mice had significantly diminished increases in systemic and renal pro-inflammatory cytokines, malondialdehyde, structural alterations, and decline in renal function than the wild-type mice following ligation of the left coronary artery. Cardiac function and survival rates were also significantly better in the LOX-1 knockout mice than in the wild-type mice. Hence, severe myocardial ischemia results in renal dysfunction and histological abnormalities suggestive of acute renal injury. Thus, LOX-1 is a key modulator among multiple mechanisms underlying renal dysfunction following extensive myocardial infarction.
Insights
Myocardial infarction impairs kidney function, causing inflammation and damage. Blocking the LOX-1 receptor in mice significantly protected kidneys and improved heart health after heart attacks.
Area of Science:
- Cardiovascular Science
- Renal Physiology
- Inflammation Research
Background:
- Acute myocardial infarction (AMI) is known to impact renal function.
- The precise mechanisms linking AMI to kidney dysfunction remain incompletely understood.
Purpose of the Study:
- To investigate the impact of extensive myocardial infarction on renal function and histology in a mouse model.
- To elucidate the role of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in mediating renal dysfunction following AMI.
Main Methods:
- Induction of myocardial infarction via permanent ligation of the left coronary artery in mice.
- Assessment of systemic and renal inflammatory markers (cytokines, malondialdehyde).
- Evaluation of renal function (e.g., creatinine clearance, BUN), histology (fibrosis, glomerular/tubular swelling), and gene/protein expression (LOX-1, IL-1β, VCAM-1).
- Comparison between wild-type and LOX-1 knockout mice.
Main Results:
- Myocardial infarction led to increased pro-inflammatory cytokines and lipid peroxidation, followed by significant renal function decline, fibrosis, and histological damage by Day 3.
- Increased expression of LOX-1, IL-1β, VCAM-1, and thiobarbituric acid-reactive substances was observed in the kidneys.
- LOX-1 knockout mice exhibited attenuated systemic/renal inflammation, reduced oxidative stress, preserved renal function, and improved cardiac function and survival compared to wild-type mice.
- Renal function showed partial recovery by Day 21, but progressive fibrosis persisted.
Conclusions:
- Extensive myocardial infarction induces acute renal injury, characterized by inflammation, oxidative stress, and histological abnormalities.
- LOX-1 plays a critical role in mediating renal dysfunction and adverse outcomes following myocardial infarction.
- Targeting LOX-1 may represent a therapeutic strategy to mitigate kidney damage in patients with myocardial infarction.
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