Assessment of MMP-9, TIMP-1, and COX-2 in normal tissue and in advanced symptomatic and asymptomatic carotid plaques

<p>Abstract</p> <p>Background</p> <p>Mature carotid plaques are complex structures, and their histological classification is challenging. The carotid plaques of asymptomatic and symptomatic patients could exhibit identical histological components.</p> <p>Objectives</p> <p>To investigate whether matrix metalloproteinase 9 (MMP-9), tissue inhibitor of MMP (TIMP), and cyclooxygenase-2 (COX-2) have different expression levels in advanced symptomatic carotid plaques, asymptomatic carotid plaques, and normal tissue.</p> <p>Methods</p> <p>Thirty patients admitted for carotid endarterectomy were selected. Each patient was assigned preoperatively to one of two groups: group I consisted of symptomatic patients (n = 16, 12 males, mean age 66.7 ± 6.8 years), and group II consisted of asymptomatic patients (n = 14, 8 males, mean age 67.6 ± 6.81 years). Nine normal carotid arteries were used as control. Tissue specimens were analyzed for fibromuscular, lipid and calcium contents. The expressions of MMP-9, TIMP-1 and COX-2 in each plaque were quantified.</p> <p>Results</p> <p>Fifty-eight percent of all carotid plaques were classified as Type VI according to the American Heart Association Committee on Vascular Lesions. The control carotid arteries all were classified as Type III. The median percentage of fibromuscular tissue was significantly greater in group II compared to group I (<it>p </it>< 0.05). The median percentage of lipid tissue had a tendency to be greater in group I than in group II (<it>p </it>= 0.057). The percentages of calcification were similar among the two groups. MMP-9 protein expression levels were significantly higher in group II and in the control group when compared with group I (p < 0.001). TIMP-1 expression levels were significantly higher in the control group and in group II when compared to group I, with statistical difference between control group and group I (p = 0.010). COX-2 expression levels did not differ among groups. There was no statistical correlation between MMP-9, COX-2, and TIMP-1 levels and fibrous tissue.</p> <p>Conclusions</p> <p>MMP-9 and TIMP-1 are present in all stages of atherosclerotic plaque progression, from normal tissue to advanced lesions. When sections of a plaque are analyzed without preselection, MMP-9 concentration is higher in normal tissues and asymptomatic surgical specimens than in symptomatic specimens, and TIMP-1 concentration is higher in normal tissue than in symptomatic specimens.</p

Vascular Stenosis: An Introduction

International audienceAn arterial stenosis is a narrowing of the lumen that disturbs the local blood flow and precludes the adequate irrigation of perfused organs. A vascular stenosis can be extrinsic, which is caused by external compression (e.g., aneurysms and tumors), or intrinsic, currently related to atherosclerosis.Atherosclerosis is defined by an intramural retention of lipids coupled to inflammation and dyslipidemia. Atherosclerosis scatters throughout large and medium thick-walled systemic arteries, especially near and in branching regions. (Pulmonary arterial stenosis is a congenital defect.)Atherosclerosis is characterized by migration from the media, proliferation, and dedifferentiation of vascular smooth myocytes in the subendothelial layer, in addition to monocyte diapedesis and differentiation into macrophages. Both smooth myocytes and macrophages scavenge accumulated oxidized low-density lipoproteins (oxLDL) and transform into foam cells. Atherosclerosis produces symptoms when the arterial lumen is severely narrowed.Advanced atherosclerotic plaques can be destabilized, thereby being a source of clotting and subsequent emboli. Emboli block tissue perfusion in a smaller downstream artery, thereby causing ischemia and infarction.The treatment of stenotic arterial segments relies on surgical grafting or medical minimally invasive procedures such as stenting. However, both methods often lead to intimal hyperplasia resulting from uncontrolled proliferation of vascular smooth myocytes. Whereas atheroma evolves during a time magnitude order of 10 years, posttherapeutic intimal hyperplasia develops in a period of order 1 month.Successful stenting can be assumed as a procedure without strong endothelial injury. In other words, both delayed thrombosis and intimal hyperplasia result from stent deployment that more or less severely damages the vascular endothelium. To eliminate these complications, drug-eluting stents have been designed and fabricated. However, the antiproliferative drug not only blocks vascular smooth myocyte division but also precludes endothelium healing. In the absence of proper endothelial interface between blood and arterial wall, that is, when the local controller of blood coagulation and cell proliferation is missing, thrombosis and restenosis occur.Arterial stenoses have stimulated biomechanicians and applied mathematicians. They carried out flow visualization and pressure and velocity measurements in experimental models of stenoses with idealized, symmetrical or not, geometry. In parallel to technological improvements of medical imaging techniques, computational fluid dynamics, due to new numerical schemes and high-performance computing, enables to perform numerical tests on subject-specific compartments of the blood circulation, after 3D reconstruction, rather than focusing on more or less short arterial, branched or not, segments. In addition, the drug release from drug-eluting stents is investigated using mathematical models