Kefir peptides alleviate high-fat diet-induced atherosclerosis by attenuating macrophage accumulation and oxidative stress in ApoE knockout mice

Abstract

In the past decade, the high morbidity and mortality of atherosclerotic disease have been prevalent worldwide. High-fat food consumption has been suggested to be an overarching factor for atherosclerosis incidence. This study aims to investigate the effects of kefir peptides on high-fat diet (HFD)-induced atherosclerosis in apolipoprotein E knockout (ApoE −/−) mice. 7-week old male ApoE −/− and normal C57BL/6 mice were randomly divided into five groups (n = 8). Atherosclerotic lesion development in ApoE −/− mice was established after fed the HFD for 12 weeks compared to standard chow diet (SCD)-fed C57BL/6 and ApoE −/− control groups. Kefir peptides oral administration significantly improved atherosclerotic lesion development by protecting against endothelial dysfunction, decreasing oxidative stress, reducing aortic lipid deposition, attenuating macrophage accumulation, and suppressing the inflammatory immune response compared with the HFD/ApoE −/− mock group. Moreover, the high dose of kefir peptides substantially inhibited aortic fibrosis and restored the fibrosis in the aorta root close to that observed in the C57BL/6 normal control group. Our findings show, for the first time, anti-atherosclerotic progression via kefir peptides consumption in HFDfed ApoE −/− mice. The profitable effects of kefir peptides provide new perspectives for its use as an antiatherosclerotic agent in the preventive medicine. The World Health Organization (WHO) suggests that cardiovascular diseases (CVDs) are the primary cause of mortality, and considerably more individuals die annually from CVDs than from any other cause globally. Atherosclerosis is known as the major cause of CVDs. The pivotal initiators involved in atherosclerosis development are enhanced levels of low-density lipoprotein (LDL) cholesterol in the circulation, vascular reactive oxygen species (ROS) generation, and inflammation 1. It has been suggested that inflammation plays a fundamental role in CVDs and atherosclerotic lesion progression 2. In early atherosclerotic lesions, the accumulation of foam cells leads to fatty streak formation. Immune cells and vascular smooth muscle cells (VSMCs) accumulate in the subendothelial layer of the artery wall 3,4. Various inflammatory cells, including neutrophils, macrophages, and lymphocytes, are involved in atherosclerosis progression; however, macrophages were reported as the first inflammatory cell associated with atherosclerosis and predominantly present within atherosclerotic vessels 5-7 .

Kefir and Intestinal Microbiota Modulation: Implications in Human Health

“…Moreover, kefir prevented the endothelial adhesion of monocytes, decreasing the evolution of the atherosclerotic lesion. These results indicate that the consumption of kefir could be useful in the prevention and treatment of atherosclerosis ( 40 ).…”

“…Tung et al ( 40 ) evaluated the effect of kefir peptides in Apo E –/– mice with high-fat diet-induced atherosclerosis ( Table 1 ). After a 12-week intervention, the consumption of kefir led to a decrease in the evolution of atherosclerotic lesions, with less lipid deposition at the root of the aorta and suppression of the inflammatory immune response, through a reduction in oxidative stress, the accumulation of macrophages and the release of IL-1β and TNF-α cytokines.…”

Kefir and Its Biological Activities

“…The study indicated that the kefir inhibits the induced inflammation and improves the state of oxidative stress. A recent study by Tung et al [128] reported the effects of kefir peptides on high-fat diet-induced atherosclerosis in apolipoprotein E knockout mice. The kefir peptides treatment has significantly improved the development of atherosclerotic lesion by attenuating oxidative stress, macrophage accumulation, endothelial dysfunction, aortic lipid deposition, and inflammatory immune response.…”

The Emerging Scenario of the Gut–Brain Axis: The Therapeutic Actions of the New Actor Kefir against Neurodegenerative Diseases

“…These potentially beneficial compounds were yielded during the fermentation process, including lactic and acetic acids, vitamins, volatile compounds, nutraceutical components, and, especially, small peptides derived from milk proteins, including “captopril-like effects” [ 9 , 164 ]. Recently, many studies have reported the important role of kefir, most of which associate bioactive compounds with the antioxidant and/or anti-inflammatory properties of beverages [ 163 , 182 , 203 , 204 , 205 ].…”