ABSTRACT
BACKGROUND: Complications deriving from arterial aneurysm and dissection without signs of atherosclerosis are rare clinical entities. In recent literature case reports show a descriptive similarity of pathological findings summarized as segmental arterial mediolysis (SAM). OBJECTIVE: The purpose of this study was to answer the question whether, among 16 patients suffering from SAM histological findings corresponded and assess causality. MATERIALS AND METHODS: In a prospective prognostic trial sixteen patients were enrolled between 1st January 2008 and 31st October 2011. Inclusion criteria were a lack of atherosclerosis, age under 60 and clinical findings. Most of these sixteen patients were treated as emergency cases of life-threatening blood loss or organ system ischemia. Thirteen of the patients were male, 3 female and their average age was 44 (28-59) years. Localisation of the segmental aneurysm or dissection showed a broad variability from central to renovisceral and peripheral lesions. Imaging diagnostics (e.g., US and CT-A) were complemented by exclusion of positive family history, connective tissue diseases and autoimmune or inflammative disorders. In 8 patients with open vascular reconstructions, it was possible to obtain a biopsy from the target lesion to analyse morphological and immunochemical expression levels (e.g., MMP1-12, vWF, vSMC or CD 68). RESULTS: None of the patients died nor had described familiar associations. Even the examination of twins with sCAD showed no coincidence. Differential diagnostic findings were excluded. All patients agreed to undergo human genetic screening. The 8 biopsy tissues showed homogeneously mediolysis with focal and increasingly confluent lesions. Main findings were that the vessel wall layering was destroyed and that capillarisation was initiated from the adventitial layer. Furthermore, all patients suffered from hypertension associated to the SAM, or developed it during surveillance. CONCLUSION: SAM is a rare, life-threatening diagnosis and has to be taken into consideration in young patients with aneurysm and dissection of unusual locations. Rare vascular diseases should have a forum in future investigations which might highlight molecular genetic triggers and associated diseases, e.g., hypertension and aortic type B dissection.
Subject(s)
Aneurysm/diagnosis , Aortic Dissection/diagnosis , Peripheral Arterial Disease/diagnosis , Tunica Media/pathology , Actins/analysis , Adult , Aortic Dissection/etiology , Aortic Dissection/pathology , Aortic Dissection/therapy , Antigens, CD/analysis , Antigens, Differentiation, Myelomonocytic/analysis , Biopsy , Female , Granulocyte-Macrophage Colony-Stimulating Factor/analysis , Humans , Metalloproteases/analysis , Middle Aged , Peripheral Arterial Disease/etiology , Peripheral Arterial Disease/pathology , Peripheral Arterial Disease/therapy , Prognosis , Prospective Studies , von Willebrand Factor/analysisABSTRACT
Vascular remodeling is influenced by trauma and proatherogenic factors such as cholesterol. It has been shown that cholesterol exerts a direct effect on vessel wall structure. In this study we evaluated the effects of vascular trauma and cholesterol treatment on vascular remodeling and plaque integrity in carotid ligated ApoE-deficient mice. The right carotid artery was ligated in mice fed regular chow or cholesterol and fat containing diet. After 4 weeks left (non-ligated) and right (ligated) carotids were prepared. For studying vascular remodeling the vascular areas were evaluated morphometrically by calculating the areas from circumference measurements on Verhoff-van Gieson stains. The cellular and structural features of the plaque were analyzed by histological staining and immunohistochemistry. Under regular chow total vessel area decreased by 35% (p<0.001); cholesterol-rich diet led to an increase by 20% (p<0.05). In both feeding groups ligated carotids presented neointima development. The medial area increased only in mice fed regular chow. The luminal area was reduced by 80% (regular chow: p<0.001) and by 90% (cholesterol-rich diet: p<0.01). Regular chow led to structured plaques showing the typical features of stable plaques. Under cholesterol diet well defined plaque structures were missing. These lesions were characterized by numerous macrophages, few mostly PCNA positive smooth muscle cell (SMC) and less collagen particularly in the shoulder region. Our data indicate that in ApoE-deficient mice both direction of the remodeling response and lesion integrity are due to the diet applied: regular chow led to constrictive remodeling, whereas cholesterol and fat containing diet was associated with an adaptive response. Our data further indicate that the direction of response is not only related to the macrophage content but also to a proliferative intimal SMC-phenotype. Our data implicate that high serum cholesterol levels are not only inducers of plaque instability but also of the so far "positively recorded" compensatory remodeling.
