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Stroke-prone SHR and arteriolipidosis-prone SHR as models for atherosclerosis: their mechanisms and application for
1World Health Organization Collaborating Centre for Research on Primary Prevention of Cardiovascular Diseases, Life Science, Kyoto University, Japan.
Abstract:
1. Peritoneal macrophages (Mphi) were harvested from non-stimulated 2 month old SHRSP and WKY, and incubated with acetyl LDL or [14C]-oleate-albumin complex to check total, free and esterified cholesterol (Cho) accumulation as well as acy coenzyme A-cholesterol acyltransferase (ACAT) activity and its activation by hyperlipidaemic serum. 2. Total and esterified Cho accumulation as well as ACAT activity were enhanced in Mphi from SHRSP compared with those from WKY. 3. To observe the dietary or pharmacological influence on atherogenesis, arteriolipidosis-prone SHR (ALR) were given a high fat cholesterol diet with 3% taurine or a Ca blocker (Nilvadipine, N; 30 mg/kg), both of which significantly decreased serum Cho level and clearly attenuated arterial fat deposition.
Insights
Macrophages from SHRSP rats show higher cholesterol accumulation and ACAT activity than WKY rats. Dietary or pharmacological interventions reduced serum cholesterol and arterial fat deposition in atherogenesis-prone SHR.
Area of Science:
- Cardiovascular Science
- Biochemistry
- Pharmacology
Background:
- Hypertension and hyperlipidemia are key risk factors for atherosclerosis.
- Macrophages play a crucial role in the development of atherosclerotic lesions.
- Spontaneously hypertensive stroke-prone (SHRSP) rats are a valuable model for studying cardiovascular diseases.
Purpose of the Study:
- To investigate cholesterol metabolism and ACAT activity in peritoneal macrophages from SHRSP and WKY rats.
- To evaluate the effects of dietary and pharmacological interventions on atherogenesis in SHR.
- To assess the impact of taurine and a calcium channel blocker on serum cholesterol and arterial fat deposition.
Main Methods:
- Peritoneal macrophages were isolated from SHRSP and WKY rats.
- Macrophages were incubated with acetylated LDL or [14C]-oleate-albumin complex.
- Cholesterol accumulation, ACAT activity, and its activation were measured.
- Arteriolipidosis-prone SHR (ALR) were fed a high-fat, high-cholesterol diet supplemented with taurine or nilvadipine.
Main Results:
- Macrophages from SHRSP rats exhibited significantly higher total and esterified cholesterol accumulation compared to WKY rats.
- ACAT activity and its activation by hyperlipidemic serum were also enhanced in SHRSP macrophages.
- Dietary taurine and pharmacological nilvadipine treatment significantly reduced serum cholesterol levels in ALR rats.
- Both interventions effectively attenuated arterial fat deposition in ALR rats.
Conclusions:
- SHRSP rat macrophages display an enhanced capacity for cholesterol accumulation and ACAT activity, contributing to atherogenesis.
- Dietary and pharmacological interventions targeting serum cholesterol can effectively mitigate arterial lipid deposition in a relevant animal model.
- These findings highlight potential therapeutic strategies for managing atherosclerosis in hypertensive individuals.