Ketosis prevents abdominal aortic aneurysm rupture through C-C chemokine receptor type 2 downregulation and enhanced extracellular matrix balance.
Ketosis prevents abdominal aortic aneurysm rupture through C-C chemokine receptor type 2 downregulation and enhanced extracellular matrix balance.
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DOI：
10.1038/s41598-024-51996-7
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发表时间：
2024-01-16
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
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腹主动脉瘤（AAA）随着年龄的增长而流行，AAA破裂与死亡率增加相关。目前没有有效的药物治疗来预防AAA破裂。单核细胞趋化蛋白（MCP-1）/C-C趋化因子受体2型（CCR 2）轴关键地调节AAA炎症、基质金属蛋白酶（MMP）产生和细胞外基质（ECM）稳定性。因此，我们假设可以调节CCR 2轴的饮食干预可能在治疗上影响AAA破裂的风险。由于酮体（KBs）可以触发炎症反应的修复机制，我们评估了体内全身性酮症是否可以减少CCR 2和AAA进展。雄性Sprague-Dawley大鼠使用猪胰弹性蛋白酶进行AAA形成手术，并每日接受β-氨基丙腈以促进AAA破裂。AAA大鼠接受标准饮食、生酮饮食（KD）或外源性KB（EKB）。接受KD和EKB的大鼠达到酮症状态，并且AAA扩张和破裂发生率显著降低。酮症还导致主动脉CCR 2含量显著降低，MMP平衡改善，ECM降解减少。与这些发现一致，我们还观察到Ccr 2 −/−小鼠显著减少了AAA扩张和破裂。总之，这项研究表明，CCR 2是AAA扩张所必需的，并且其与酮症的调节可以减少AAA病理。这为未来的临床研究提供了动力，这些研究将评估酮症对人类AAA疾病的影响。
Abdominal aortic aneurysms (AAAs) are prevalent with aging, and AAA rupture is associated with increased mortality. There is currently no effective medical therapy to prevent AAA rupture. The monocyte chemoattractant protein (MCP-1)/C–C chemokine receptor type 2 (CCR2) axis critically regulates AAA inflammation, matrix-metalloproteinase (MMP) production, and extracellular matrix (ECM) stability. We therefore hypothesized that a diet intervention that can modulate CCR2 axis may therapeutically impact AAA risk of rupture. Since ketone bodies (KBs) can trigger repair mechanisms in response to inflammation, we evaluated whether systemic ketosis in vivo could reduce CCR2 and AAA progression. Male Sprague–Dawley rats underwent surgical AAA formation using porcine pancreatic elastase and received daily β-aminopropionitrile to promote AAA rupture. Rats with AAAs received either a standard diet, ketogenic diet (KD), or exogenous KBs (EKB). Rats receiving KD and EKB reached a state of ketosis and had significant reduction in AAA expansion and incidence of rupture. Ketosis also led to significantly reduced aortic CCR2 content, improved MMP balance, and reduced ECM degradation. Consistent with these findings, we also observed that Ccr2−/− mice have significantly reduced AAA expansion and rupture. In summary, this study demonstrates that CCR2 is essential for AAA expansion, and that its modulation with ketosis can reduce AAA pathology. This provides an impetus for future clinical studies that will evaluate the impact of ketosis on human AAA disease.
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DOI：
10.1042/cs20090372
发表时间：
2010-03-09
期刊：
Clinical science (London, England : 1979)
影响因子：
--
作者：
Daugherty A;Rateri DL;Charo IF;Owens AP;Howatt DA;Cassis LA
通讯作者：
Cassis LA
DOI：
10.1056/nejm197003052821026
发表时间：
1970-03-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Cahill, G F Jr
通讯作者：
Cahill, G F Jr
影响因子：
3.8
作者：
Wang SK;Green LA;Gutwein AR;Drucker NA;Motaganahalli RL;Gupta AK;Fajardo A;Murphy MP
通讯作者：
Murphy MP
影响因子：
5.6
作者：
Gregoretti, IV;Lee, YM;Goodson, HV
通讯作者：
Goodson, HV
DOI：
10.1164/rccm.202004-1132oc
发表时间：
2021-01-01
影响因子：
24.7
作者：
Brody, Steven L.;Gunsten, Sean P.;Liu, Yongjian
通讯作者：
Liu, Yongjian