Abstract
Glucagon-like peptide-1 (GLP-1) regulates processes involved in the pathophysiology of thoracic aortic aneurysms (TAAs), including inflammation, while protecting against aortic aneurysms in animal models. Type 2 diabetes (T2D) involves altered GLP-1 signaling due to pathology and/or therapy and is associated with reduced prevalence of TAAs. We aimed to assess whether T2D alters the inflammatory profile/proteolytic activity, possible correlations to elevated fasting GLP-1 (F-GLP-1), and its relevance for TAA. F-GLP-1, pro-inflammatory T helper 1 (Th1) cytokines, Th2 cytokines, C-reactive protein, and matrix metalloproteinase-2 activity (MMP-2) were analyzed in surgical patients with aortic valve pathology with/without T2D and without T2D but with TAA. Patients with T2D displayed an increase in the relative systemic expression of interleukin 6 and tumor necrosis factor α and a clear trend towards reduced levels of interferon γ (IFNγ). In addition, a positive association between GLP-1 and the plasma interleukin 4 (IL-4)/IFNγ ratio was detected. TAA was associated with significantly lower plasma levels of the Th2 cytokines IL-4 and interleukin 5. Plasma MMP-2 activity did not differ between groups. We conclude that T2D involved a Th2 shift, which associates with elevated F-GLP-1 and may—considering Th1 bias in TAA—contribute to reduced prevalence of TAA in T2D.
Highlights
Thoracic aortic aneurysms (TAA) are balloon-like dilations of the aorta above the diaphragm, caused by a weakening of the aortic wall
Altered plasma matrix metalloproteinase-2 activity (MMP-2) activity was not associated with type 2 diabetes (T2D) (Supplementary Materials, Figure S3A) or F-Glucagon-like peptide-1 (GLP-1) (Supplementary Materials, Figure S3B,C, respectively), a negative association with tumor necrosis factor α (TNF-α) was observed in the T2D group (r = −0.5746, p < 0.05, Figure 3f)
Enhanced GLP-1 signaling due to treatment and/or pathology may contribute to a reduced prevalence of TAAs in T2D, possibly through regulation of inflammatory responses and/or proteolytic activity [18]
Summary
Thoracic aortic aneurysms (TAA) are balloon-like dilations of the aorta above the diaphragm, caused by a weakening of the aortic wall. One of the largest studies to date, found an overall pooled risk reduction of 15% for TAAs and AAAs among patients with T2D, as compared with controls [4] Another longitudinal observational study of nearly three million individuals found a relative risk reduction of 28% for AAs (including both TAAs and AAAs) and 44% for TAAs [5]. None of these studies considered anti-diabetic therapy when assessing the prevalence of TAA in T2D, and the risk reduction conferred by T2D may involve pathophysiological mechanisms and/or effects of antidiabetic therapy. Unraveling the factors/mechanisms contributing to the protective effect of T2D may contribute to a first future pharmacological intervention in TAA, which is increasing in prevalence and is a critical condition, despite modern diagnostic tools and current surgical/endovascular repair
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