Cytokines and atherosclerosis: A comprehensive review of studies in mice

In the past few years, inflammation has emerged as a major driving force of atherosclerotic lesion development. It is now well-established that from early lesion to vulnerable plaque formation, numerous cellular and molecular inflammatory components participate in the disease process. The most prominent cells that invade in evolving lesions are...

Activation of the innate immune system in atherosclerotic disease

Innate immunity is the first line of defence against invading micro-organisms. The family of Toll-like receptors (TLRs) recognizes pathogen-associated molecular patterns (PAMPs) that are carried by the invading micro-organisms. Infectious pathogens have been implicated to play an important role in atherosclerosis. Nowadays, evidence is...

Apolipoprotein C-I is crucially involved in lipopolysaccharide-induced atherosclerosis development in apolipoprotein E-knockout mice

BACKGROUND - Lipopolysaccharide (LPS), which is released from Gram-negative bacteria on multiplication or lysis, aggravates atherosclerosis in humans and rodents by inducing inflammation via toll-like receptors. Because apolipoprotein C-I (apoCI) enhances the LPS-induced inflammatory response in macrophages in vitro and in mice, we investigated...

Fenofibrate reduces atherogenesis in ApoE*3Leiden mice: Evidence for multiple antiatherogenic effects besides lowering plasma cholesterol

OBJECTIVE - To demonstrate, quantify, and mechanistically dissect antiatherosclerotic effects of fenofibrate besides lowering plasma cholesterol per se. METHODS AND RESULTS - ApoE*3Leiden transgenic mice received either a high-cholesterol diet (HC) or HC containing fenofibrate (HC+FF) resulting in 52% plasma cholesterol-lowering. In a separate...

Macrophage low-density lipoprotein receptor-related protein deficiency enhances atherosclerosis in apoE/LDLR double knockout mice

OBJECTIVE - In vitro studies implicate that the low-density lipoprotein receptor (LDLR)-related protein (LRP) in macrophages has a pro-atherogenic potential. In the present study, we investigated the in vivo role of macrophage specific LRP in atherogenesis independent of its role in the uptake of lipoproteins. METHODS AND RESULTS - We generated...

No effect of C-reactive protein on early atherosclerosis development in apolipoprotein E*3-Leiden/human C-reactive protein transgenic mice

Objective - C-reactive protein (CRP) has been associated with risk of cardiovascular disease. It is not clear whether CRP is causally involved in the development of atherosclerosis. Mouse CRP is not expressed at high levels under normal conditions and increases in concentration only several-fold during an acute phase response. Because the...

Hepatic low-density lipoprotein receptor-related protein deficiency in mice increases atherosclerosis independent of plasma cholesterol

The low-density lipoprotein (LDL) receptor-related protein (LRP) has a well-established role in the hepatic removal of atherogenic apolipoprotein E (APOE)-rich remnant lipoproteins from plasma. In addition, LRP recognizes multiple distinct pro- and antiatherogenic ligands in vitro. Here, we investigated the role of hepatic LRP in atherogenesis...

Evidence for anti-inflammatory activity of statins and PPARα activators in human C-reactive protein transgenic mice in vivo and in cultured human hepatocytes in vitro

Inflammatory processes, aside from cholesterol, play a central role in atherogenesis. Human C-reactive protein (huCRP) signals systemic inflammation and independently predicts future cardiovascular risk. Cholesterol-lowering statins reduce atherosclerosis and plasma huCRP levels. Evidence is sought for a direct anti-inflammatory statin effect in...

Induction of atherosclerotic plaque rupture in apolipoprotein E-/- mice after adenovirus-mediated transfer of p53

Background - The presence of the tumor-suppressor gene p53 in advanced atherosclerotic plaques and the sensitivity to p53-induced cell death of smooth muscle cells isolated from these plaques have fueled speculation about the role of p53 in lesion destabilization and plaque rupture. In this study, we describe a strategy to promote (thrombotic)...

Omega-3 fatty acids in adipose tissue and risk of myocardial infarction: The EURAMIC study

Omega-3 fatty acids have potential antiatherogenic, antithrombotic, and antiarrhythmic properties, but their role in coronary heart disease remains controversial. To evaluate the association of omega-3 fatty acids in adipose tissue with the risk of myocardial infarction in men, a case-control study was conducted in eight European countries and...

Macrophage specific overexpression of the human macrophage scavenger receptor in transgenic mice, using a 180-kb yeast artificial chromosome, leads to enhanced foam cell formation of isolated peritoneal macrophages

Macrophage scavenger receptors class A (MSR) are thought to play an important role in atherogenesis by mediating the unrestricted uptake of modified lipoproteins by macrophages in the vessel wall leading to foam cell formation. To investigate the in vivo role of the MSR in this process, a transgenic mouse model expressing both isoforms of the...

Seasonal variation in low density lipoprotein oxidation and antioxidant status

Fibrinogen and atherosclerosis: A study in transgenic mice

Atherosclerosis is a multifactorial disease that is influenced by both genetic and environmental factors. Recent epidemiological studies have shown that the combination of elevated VLDL/LDL concentrations and elevated fibrinogen levels results in a strong increase of the risk for cardiovascular disease as compared to the individual risk factors....

Autoantibodies against MDA-LDL in subjects with severe and minor atherosclerosis and healthy population controls

Autoantibodies against oxidized low-density lipoprotein (LDL) have been reported to be associated with atherosclerosis. However, data are not consistent. We compared the titres of autoantibodies to malondialdehyde-modified LDL in three groups, a case group with angiographically documented severe coronary stenosis (> 80% stenosis in at least 1...

Sex steroids and lipoprotein metabolism

Lipoprotein metabolism is involved in atherogenesis. Female sex-hormones have substantial effects on both lipoprotein metabolism and the vessel wall. Cholesterol, one of the major lipids in lipoproteins, is both the substrate for, and the target of, the steroidal sex hormones.