Abstract
BackgroundType 1 diabetes (T1D) is a major risk factor for cardiovascular disease (CVD). Matrix metalloproteinase-14 (MMP-14) is involved in the development of atherosclerosis and CVD. The main aim was to explore the associations between MMP-14 and selected inflammatory and metabolic variables, CVD, depression, physical activity, smoking and medication in patients with T1D. The secondary aim was to explore associations with CVD.MethodsCross-sectional design. The participants were consecutively recruited from one specialist diabetes out-patient clinic. Depression was assessed by a self-report instrument. Blood samples, anthropometrics and blood pressure were collected, supplemented with data from electronic health records. High MMP-14 was defined as ≥ 5.81 ng/mL. Non-parametric tests, Chi2 tests and multiple logistic regression analyses were performed.ResultsTwo hundred and sixty-eighth T1D patients aged 18–59 years participated (men 58%, high MMP-14 25%, CVD 3%). Sixty-seven patients with high MMP-14, compared to 201 patients with lower MMP-14, had higher prevalence of CVD (8% versus 1%, p = 0.012), and had higher levels of galectin-3 (p < 0.001) and MMP-2 (p = 0.018). Seven patients with CVD, compared to 261 without, were older (p = 0.003), had longer diabetes duration (p = 0.027), and had higher prevalence of high MMP-14 (71% versus 24%, p = 0.012), abdominal obesity (p = 0.014), depression (p = 0.022), usage of antidepressants (p = 0.008), antihypertensive drugs (p = 0.037) and statins (p = 0.049).Galectin-3 (per ng/mL) [adjusted odds ratio (AOR) 2.19, p < 0.001], CVD (AOR 8.1, p = 0.027), and MMP-2 (per ng/mL) (AOR 1.01, p = 0.044) were associated with high MMP-14. Depression (AOR 17.4, p = 0.006), abdominal obesity (15.8, p = 0.006), high MMP-14 (AOR 14.2, p = 0.008), and diabetes duration (AOR 1.10, p = 0.012) were associated with CVD.ConclusionsThe main findings of this study were that galecin-3, MMP-2, and CVD were independently associated with high levels of MMP-14 in T1D patients. The association between MMP-14 and galectin-3 is a new finding. No traditional risk factors for CVD were associated with MMP-14. Depression, abdominal obesity and MMP-14 were independently associated with CVD.
Highlights
Type 1 diabetes (T1D) is a major risk factor for cardiovascular disease (CVD)
Depression, abdominal obesity and Matrix metalloproteinase-14 (MMP-14) were independently associated with CVD
The Area under the curve (AUC) (CI 95%) for Matrix metalloproteinases (MMPs)-14 tried against CVD was 0.75 (0.55–0.95), p = 0.023, and the cut-off value MMP14 ≥ 5.81 ng/mL corresponded to a sensitivity of 0.71 and specificity of 0.70
Summary
Matrix metalloproteinase-14 (MMP-14) is involved in the development of atherosclerosis and CVD. Matrix metalloproteinases (MMPs) are expressed in atherosclerotic plaques, promoting vascular remodelling, contributing to atherothrombosis, and plaque disruption [9, 12,13,14]. They are involved in cardiac remodelling after myocardial infarction, leading to dilated cardiomyopathy [9]. It has been demonstrated that MMP-14 is upregulated in a harmful macrophage phenotype (MMP14+TIMP3−), which contributes to increased risk for plaque rupture and myocardial infarction [14]. Decreased levels of TIMP-3 have been linked to ventricular remodelling after myocardial infarction [17]
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