Reduced expansion rate of abdominal aortic aneurysms in patients with diabetes may be related to aberrant monocyte-matrix interactions
Reduced expansion rate of abdominal aortic aneurysms in patients with diabetes may be related to aberrant monocyte-matrix interactions
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DOI：
10.1093/eurheartj/ehm557
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发表时间：
2008-03-01
影响因子：
39.3
通讯作者：
Norman, Paul E.
中科院分区：
文献类型：
--
作者：
Golledge, Jonathan;Karan, Mirko;Norman, Paul E.
糖尿病增加动脉粥样硬化血栓形成的风险，但降低腹主动脉瘤（AAA）的风险。这种差异的原因尚不清楚。我们研究的作用，糖尿病和糖化对AAA的扩张和细胞外基质-单核细胞interactions.Methods和结果，我们遵循198例（20糖尿病）谁有30-45毫米AAA每年主动脉超声3年。糖尿病与AAA生长减少独立相关（β =-0.17，P = 0.01;扩张的OR高于中位数0.18，95%置信区间0.06-0.57）。在体外孵育的人单核细胞与糖化牛血清白蛋白或单体I型胶原增加基质金属蛋白酶（MMP）的分泌。与此相反，暴露活化的单核细胞糖化I型胶原晶格诱导MMP和白细胞介素-6分泌显着减少。这种去活化作用也在交联的非糖化胶原蛋白晶格、健康的脱细胞主动脉介质和来自患有动脉粥样硬化的糖尿病患者的脱细胞主动脉介质中得到证实。相比之下，患有动脉粥样硬化但没有糖尿病的患者的脱细胞主动脉中膜诱导了MMP分泌增加。结论这些发现证实了糖尿病患者AAA的进展较慢，并提出了一种保护主动脉中膜免受降解的机制。在这些人中。
Aims Diabetes increases the risk of atherothrombosis, but reduces the risk of abdominal aortic aneurysm (AAA). The reason for this difference is unknown. We examined the role of diabetes and glycation on AAA expansion and extracellular matrix-monocyte interactions.Methods and results We followed 198 patients (20 with diabetes) who had 30-45 mm AAAs with yearly aortic ultrasound for 3 years. Diabetes was independently associated with reduced AAA growth (beta = -0.17, P = 0.01; OR for expansion above median 0.18, 95% confidence interval 0.06-0.57). In vitro incubation of resting human monocytes with glycated bovine serum albumin or monomeric type I collagen increased matrix metalloproteinase (MMP) secretion. In contrast, exposure of activated monocytes to glycated type I collagen lattices induced a marked reduction in MMP and interleukin-6 secretion. This de-activating effect was also demonstrated in cross-linked non-glycated collagen lattices, healthy decellularized aortic media, and decellularized aortic media from diabetes patients with atherosclerosis. In contrast, decellularized aortic media from patients with atherosclerosis, but no diabetes, induced increased MMP secretion.Conclusion These findings confirm that the progression of AAA is slower in patients with diabetes and suggest a mechanism by which the aortic media may be protected from degradation in these individuals.