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Submitted: 11 Dec 2018
Accepted: 10 Jan 2020
ePublished: 30 Jan 2020
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J Cardiovasc Thorac Res. 2020;12(1): 43-50.
doi: 10.34172/jcvtr.2020.07
PMID: 32211137
PMCID: PMC7080336
  Abstract View: 146
  PDF Download: 113

Original Article

Oxidized cholesterol exacerbates toll-like receptor 4 expression and activity in the hearts of rats with myocardial infarction

Arash Khorrami 1,2 ORCID logo, Mojtaba Ziaee 1,3 * ORCID logo, Maryam Rameshrad 4,2, Ailar Nakhlband 5,2 ORCID logo, Nasrin Maleki-Dizaji 2 ORCID logo, Alireza Garjani 2 * ORCID logo

1 Medicinal Plants Research Center, Maragheh University of Medical Sciences, Maragheh, Iran
2 Department of Pharmacology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
3 Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
4 Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran
5 Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran
*Corresponding Author: Mojtaba Ziaee, Email: mjziaee@gmail.com; Alireza Garjani, mjziaee@gmail.com

Abstract

Introduction: The present study examined the effects of high cholesterol and high oxidized-cholesterol diets on the myocardial expression of TLR4 and pro-inflammatory cytokine in rats.
Methods: Male Wistar rats were allocated into 6 groups and fed with a normal diet, cholesterol, and oxidized-cholesterol rich diets with or without isoproterenol-induced myocardial infarction. TLR4 and MyD 88 expression and levels tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) were measured in the heart and serum.
Results: Oxidized cholesterol-fed animals had higher serum levels of oxidized low-density lipoprotein (LDL) (263 ± 13 ng/dL) than the cholesterol-fed animals (98 ± 8 ng/dL; P < 0.001). A high level of oxidized-LDL caused fibrotic cell formation and enhanced neutrophil infiltration in the absence of MI. Both cholesterol and oxidized-cholesterol upregulated TLR4 mRNA expression and increased TNF-α and IL-6 production in the hearts of rats with MI. In rats fed with oxidized-cholesterol the serum and myocardial levels of TNF-α (653 ± 42 pg/mL, 1375 ± 121 pg/100 mg, respectively) were higher than MI group (358±24 pg/mL, P < 0.001 and 885 ± 56 pg/100 mg, P < 0.01). A significant correlation was seen between TLR4 expression and infarct size.
Conclusion: These findings suggest that cardiac TLR4 is preferentially upregulated by oxidized cholesterol in rats. Oxidized cholesterol may have a critical role in cardiac toxicity in the absence of pathological conditions.
Keywords: Oxidized Cholesterol, Toll-Like Receptor 4, Inflammation, Myocardial Infarction, Cytokine, Rats
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