Objectives: Abdominal aortic aneurysm (AAA) wall is characterized by degradation of extracellular matrix through matrix metalloproteinases (MMPs), chronic inflammatory cell infiltration and extensive neovascularization. So far, MMP expression within AAA wall in association with infiltrates and neovascularization has not yet been studied. Methods: Vessel walls of 15 AAA patients and 8 organ donors were analyzed by immunohistochemistry for expression of various MMPs (MMP-1, -2, -3, -7, -8, -9, -12 and -13) in all cells located within the AAAs and correlated with infiltrates and neovascularization. Results: Luminal endothelial cells (ECs) were positive for MMP-1, -3 and -9, ECs of mature neovessels were furthermore positive for MMP-2. Immature neovessels expressed all MMPs tested except for MMP-13. Aortic medial smooth muscle cells (SMCs) expressed MMP-1, -2, -3 and -9, SMCs of mature neovessels, only MMP-1, -3 and -9. Inflammatory infiltrates expressed all MMPs tested except for MMP-2, macrophages expressed all MMPs. Infiltrates were composed mainly of B cells (58.5 ± 10.9%) and T lymphocytes (26.3 ± 9.5%). Furthermore, significant inverse correlations were found between the amounts of inflammatory cells, neovessels and collagen/elastin content of the aortic vessel wall (r = +0.806/p < 0.001, r = –0.650/p = 0.012, r = –0.63/p < 0.015; respectively). Conclusion: Inflammatory infiltrates and invading neovessels are relevant sources of MMPs in the AAA wall and may substantially contribute to aneurysm wall instability.

Stroke is among the major causes of mortality and disabilities in the world. About 80 % of all strokes in the anterior circulation are ischemic and up to 20 % of all ischemic strokes are caused by extracranial atherosclerotic carotid artery stenosis. The prevalence of a cervical internal carotid artery stenosis increases with age and can be found in 6.9 % of the elderly population (>65 years). Atherosclerotic changes of the carotid vessel wall can lead to plaque vulnerability and may result in arterio-arterial embolism, which frequently underlie carotid-related cerebrovascular ischemic events. Carotid atherosclerosis is characterised by inflammation, extensive degradation of extracellular matrix components, neovascularization, and as recently recognised is also affected by epigenetic changes. These factors accelerate the progression of atherosclerosis towards vulnerable plaques and increase the risk of ischemic stroke. In this review, the main pathophysiological mechanisms leading to rupture-prone carotid artery plaques and successive ischemic stroke are considered. It is important to recognise the heterogeneity of atherosclerosis and that various pathophysiological processes dissected in this review are not acting individually, but rather in a complementary manner. The identification and careful integration of all relevant factors will be required for the development of future diagnostic and therapeutic strategies.

Background: In this study a multiscore analysis of various biomarkers including matrix metalloproteinases (MMPs), inflammatory factors and other clinical parameters was performed to establish a set of reliable biomarkers for improved detection of plaque instability in patients with advanced carotid stenosis. Methods: Study patients (n = 101) were classified as histologically stable (n = 37) or unstable (n = 64). Serum levels of MMP-1, -2, -3, -7, -8, -9, MMP inhibitors TIMP-1, -2, and inflammatory factors such as tumor necrosis factor (TNF-α), interleukin (IL)-1β, -6, -8, -10, and -12 were measured by ELISA assays. Multiscore analysis was performed using multiple receiver operating characteristics analysis and determination of appropriate cutoff values. Results: Circulating levels of MMP-1, -7, TIMP-1, TNF-α, and IL-8 were significantly enhanced in patients with unstable plaques compared to individuals with stable lesions, mean differences being 1.2 (p = 0.032), 2.5 (p = 0.004), 30.0 (p = 0.014), 1.3 (p = 0.047), and 2.2 (p = 0.033), respectively. The combination of MMP-1, -7, TIMP-1 and IL-8 demonstrated the highest positive predictive value of 89.4% and negative predictive value of 60.1% for patients correctly classified as individuals with unstable and stable carotid lesions by means of blood sample analysis. Conclusions: Multiple relevant biomarkers that play a decisive role in plaque instability can improve the correct determination of vulnerable carotid plaques in patients with advanced carotid artery stenosis.

Nε-Carboxymethyllysine (CML) is the major non-cross linking advanced glycation end product (AGE). CML is elevated in diabetic patients and apparent in atherosclerotic lesions. AGEs are associated with hypertension and arterial stiffness potentially by qualitative changes of elastic fibers. We investigated whether CML affects carotid and aortic properties in normoglycemic subjects.