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- Bäck, Magnus, et al.
(författare)
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Biomechanical factors in the biology of aortic wall and aortic valve diseases
- 2013
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Ingår i: Cardiovascular Research. - : Oxford University Press. - 0008-6363 .- 1755-3245. ; 99:2, s. 232-241
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Forskningsöversikt (refereegranskat)abstract
- The biomechanical factors that result from the haemodynamic load on the cardiovascular system are a common denominator of several vascular pathologies. Thickening and calcification of the aortic valve will lead to reduced opening and the development of left ventricular outflow obstruction, referred to as aortic valve stenosis. The most common pathology of the aorta is the formation of an aneurysm, morphologically defined as a progressive dilatation of a vessel segment by more than 50% of its normal diameter. The aortic valve is exposed to both haemodynamic forces and structural leaflet deformation as it opens and closes with each heartbeat to assure unidirectional flow from the left ventricle to the aorta. The arterial pressure is translated into tension-dominated mechanical wall stress in the aorta. In addition, stress and strain are related through the aortic stiffness. Furthermore, blood flow over the valvular and vascular endothelial layer induces wall shear stress. Several pathophysiological processes of aortic valve stenosis and aortic aneurysms, such as macromolecule transport, gene expression alterations, cell death pathways, calcification, inflammation, and neoangiogenesis directly depend on biomechanical factors.
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| 2. |
- Caligiuri, Giuseppina
(författare)
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The immune response in atherosclerosis and acute coronary syndromes
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The immune system is involved in the process of atherogenesis from the earliest steps of plaque formation, throughout the progression to the mature plaque, and finally in plaque complication and clinical manifestation of plaque instability. The present study has explored the role of specific immunity in relation to clinical instability of human coronary atherosclerosis and in experimental models of atherogenesis. A systemic immune response is detectable in patients with symptomatic phases of coronary atherosclerosis (angina pectoris). A persistent activation of immune markers is detectable in patients with chronic stable angina but a transient, dramatic increase in immune activation accompanies the unstable phases of angina. The inflammatory immune response in unstable angina refractory to the medical therapy is of restricted heterogeneity and probably directed to antigens present in the culprit lesions. By contrast, the immune response observed in patients with treatment-responsive unstable angina appears in coincidence with the waning of symptoms and is not associated with rise in inflammatory markers or restriction of the T cell receptor repertoire. Hypercholesterolemic knockout mice were used to study the role of the immune response in atherogenesis. Indeed, a specific atherosclerosis-related immunity develops in parallel with lesion progression in male and female hypercholesterolemic mice and immunomodulation can profoundly affect disease progression. Importantly, the spleenassociated immune response is atheroprotective. Atheroprotection is carried by B cells and is associated with enhancement of the oxLDL-specific immune response. We also show that acute myocardial ischemia can be elicited in hypercholesterolemic knockout mice with severe coronary atherosclerosis. Therefore this is also a suitable model to study the pathogenesis of acute phases of atherosclerosis. In conclusion, our data suggest that the immune response may play both a harmful and a protective role in atherosclerosis and acute coronary syndromes. The individual immune reactivity as well as different environmental factors may account for the capacity to mount an efficient, atheroprotective immune response in some individuals or an inflammatory, atherogenic immune response in others. A selective suppression of the harmful components and an enhancement of the protective ones may open the way to new powerful therapeutic tools for the most important cause of death 'in the world.
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