Zhong Xingming, He Rong, You Shaohua, Liu Bo, Wang Xiujie, Mao Jieming
School of Kinesiology and Health, Capital University of Physical Education and Sports.
Department of Cardiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University.
Acta Cardiol Sin. 2023 Mar;39(2):309-318. doi: 10.6515/ACS.202303_39(2).20221027A.
Hyperhomocysteinemia (HHcy) is an independent risk factor for atherosclerosis. Effective interventions to reduce HHcy-accelerated atherosclerosis are required.
This study aimed to investigate the effects of aerobic exercise (AE) and folate (FA) supplementation on plasma homocysteine (Hcy) level and atherosclerosis development in a mouse model.
Six-week-old female apoE-/- mice were grouped into five groups (N = 6-8): HHcy (1.8 g/L DL-homocysteine (DL-Hcy) in drinking water), HHcy + AE (1.8 g/L DL-Hcy and aerobic exercise training on a treadmill), HHcy + FA (1.8 g/L DL-Hcy and 0.006% folate in diet), HHcy + AE + FA (1.8 g/L DL-Hcy, 0.006% folate, and aerobic exercise training on a treadmill), and a control group (regular water and diet). All treatment was sustained for 8 weeks. Triglyceride, cholesterol, lipoprotein, and Hcy levels were determined enzymatically. Plaque and monocyte chemoattractant protein-1 (MCP-1) expression levels in mouse aortic roots were evaluated by immunohistochemistry.
Compared to the HHcy group (18.88 ± 6.13 μmol/L), plasma Hcy concentration was significantly reduced in the HHcy + AE (14.79 ± 3.05 μmol/L, = 0.04), HHcy + FA (9.4 ± 3.85 μmol/L, < 0.001), and HHcy + AE + FA (9.33 ± 2.21 μmol/L, < 0.001) groups. Significantly decreased aortic root plaque area and plaque burden were found in the HHcy + AE and HHcy + AE + FA groups compared to those in the HHcy group (both < 0.05). Plasma MCP-1 level and MCP-1 expression in atherosclerotic lesions were significantly decreased in the HHcy + AE and HHcy + AE + FA groups compared to the HHcy group (all < 0.05).
AE reduced atherosclerosis development in HHcy apoE-/- mice independently of reducing Hcy levels. FA supplementation decreased plasma Hcy levels without attenuating HHcy-accelerated atherosclerosis. AE and FA supplementation have distinct mechanisms in benefiting atherosclerosis.
高同型半胱氨酸血症（HHcy）是动脉粥样硬化的独立危险因素。需要有效的干预措施来减少HHcy加速的动脉粥样硬化。
本研究旨在探讨有氧运动（AE）和补充叶酸（FA）对小鼠模型血浆同型半胱氨酸（Hcy）水平及动脉粥样硬化发展的影响。
将6周龄雌性载脂蛋白E基因敲除（apoE-/-）小鼠分为五组（每组6-8只）：HHcy组（饮用水中含1.8 g/L DL-同型半胱氨酸（DL-Hcy））、HHcy + AE组（饮用水中含1.8 g/L DL-Hcy并进行跑步机有氧运动训练）、HHcy + FA组（饮食中含1.8 g/L DL-Hcy和0.006%叶酸）、HHcy + AE + FA组（饮用水中含1.8 g/L DL-Hcy、饮食中含0.006%叶酸并进行跑步机有氧运动训练）以及对照组（饮用普通水和正常饮食）。所有处理持续8周。采用酶法测定甘油三酯、胆固醇、脂蛋白和Hcy水平。通过免疫组织化学评估小鼠主动脉根部斑块和单核细胞趋化蛋白-1（MCP-1）的表达水平。
与HHcy组（18.88±6.13 μmol/L）相比，HHcy + AE组（14.79±3.05 μmol/L，P = 0.04）、HHcy + FA组（9.4±3.85 μmol/L，P < 0.001）和HHcy + AE + FA组（9.3±2.21 μmol/L，P < 0.001）的血浆Hcy浓度显著降低。与HHcy组相比，HHcy + AE组和HHcy + AE + FA组的主动脉根部斑块面积和斑块负荷显著减小（均P < 0.05）。与HHcy组相比，HHcy + AE组和HHcy + AE + FA组的血浆MCP-1水平及动脉粥样硬化病变中的MCP-1表达均显著降低（均P < 0.05）。
有氧运动可降低HHcy apoE-/-小鼠的动脉粥样硬化发展，且与降低Hcy水平无关。补充叶酸可降低血浆Hcy水平，但并未减轻HHcy加速的动脉粥样硬化。有氧运动和补充叶酸在改善动脉粥样硬化方面具有不同机制。
