Acrolein‐induced dyslipidemia and acute‐phase response are independent of HMG‐CoA reductase

Abstract

Scope Aldehydes are ubiquitous natural constituents of foods, water and beverages. Dietary intake represents the greatest source of exposure to acrolein and related aldehydes. Oral acrolein induces dyslipidemia acutely and chronically increases atherosclerosis in mice, yet the mechanisms are unknown. Because lipid synthesis and trafficking are largely under hepatic control, we examined hepatic genes in murine models of acute and chronic oral acrolein exposure. Methods and results Changes in hepatic gene expression were examined using a Steroltalk microarray. Acute acrolein feeding modified plasma and hepatic proteins and increased plasma triglycerides within 15 min. By 6h, acrolein altered hepatic gene expression including Insig1, Insig2 and Hmgcr genes and stimulated an acute phase response (APR) with up-regulation of serum amyloid A genes (Saa) and systemic hypoalbuminemia. To test if decreased HMG-CoA reductase activity could modify acrolein-induced dyslipidemia or the APR, mice were pretreated with simvastatin. Statin treatment, however, did not alter acrolein-induced dyslipidemia or hypoalbuminemia associated with an APR. Few hepatic genes were dysregulated by chronic acrolein feeding in apoE-null mice. These studies confirmed that acute acrolein exposure altered expression of hepatic genes involved with lipid synthesis and trafficking and APR, and thus, indicated a hepatic locus of acrolein-induced dyslipidemia and APR that was independent of HMG CoA-reductase. Conclusion Dietary intake of acrolein could contribute to cardiovascular disease risk by disturbing hepatic function.

Acute effects of acrolein in human volunteers during controlled exposure

“…This suggests an up-regulation of the SAA response to acrolein in sensitive subjects. Exposure to acrolein has previously been shown to up-regulate SAA in mice (Conklin et al, 2011 ). The effect could be mediated by the receptor TRPA1 which mediates the inflammatory response to environmental irritants such as acrolein (Bautista et al, 2006 ).…”

Side Effects of Coronary Stenting such as Severe Coronary Stenosis and Multiple Coronary Chronic Total Occlusions in Elderly Patients via Induced Proinflammatory and Prooxidative Stress

“…ACR remarkably increased plasma levels of atherogenic cholesterol and low-density lipoprotein cholesterol [7]. ACR promoted cellular redox imbalance and elevated oxidative stress in cardiomyocytes, and ACR also activated the inflammatory response that elevated the risk of the development of heart disease [5, 7].…”

“…ACR remarkably increased plasma levels of atherogenic cholesterol and low-density lipoprotein cholesterol [7]. ACR promoted cellular redox imbalance and elevated oxidative stress in cardiomyocytes, and ACR also activated the inflammatory response that elevated the risk of the development of heart disease [5, 7]. ACR led to foam cell formation and accelerated the atherosclerotic plaque lesions and the development of atherosclerosis by increasing inflammatory response and inhibiting the reverse cholesterol transport process [29].…”

“…ACR promoted dysregulation of cellular cholesterol transport genes and was a key heart disease risk factor. ACR increased the cholesterol and triglyceride levels and led to cardiovascular disease and atherosclerotic lesion development [7]. Malondialdehyde (MDA) was related to inflammatory response and high levels of oxidative stress response [8, 9].…”

Aldehydes and Cardiovascular Disease

“…These effects can be either acute (rapid and short-lived) or slow in onset (e.g., transcriptional). Acute feeding of acrolein induces a pro-atherosclerotic increase in cholesterol and triglycerides Conklin et al, 2011b). For example, repeated exposure to a-ethylacrolein for 13 weeks has been found to cause cardiac hypertrophy (Appelman et al, 1981).…”