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      Antithrombotic therapy in abdominal aortic aneurysm: beneficial or detrimental?

      1 , 2 , 3 , 4 , 3 , 4
      Blood
      American Society of Hematology

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          Abstract

          Abdominal aortic aneurysm (AAA) is a degenerative vascular pathology resulting in significant morbidity and mortality in older adults due to rupture and sudden death. Despite 150 000 new cases and nearly 15 000 deaths annually, the only approved treatment of AAA is surgical or endovascular intervention when the risk for aortic rupture is increased. The goal of the scientific community is to develop novel pharmaceutical treatment strategies to reduce the need for surgical intervention. Because most clinically relevant AAAs contain a complex structure of fibrin, inflammatory cells, platelets, and red blood cells in the aneurysmal sac known as an intraluminal thrombus (ILT), antithrombotic therapies have emerged as potential pharmaceutical agents for the treatment of AAA progression. However, the efficacy of these treatments has not been shown, and the effects of shrinking the ILT may be as detrimental as they are beneficial. This review discusses the prospect of anticoagulant and antiplatelet (termed collectively as antithrombotic) therapies in AAA. Herein, we discuss the role of the coagulation cascade and platelet activation in human and animal models of AAA, the composition of ILT in AAA, a possible role of the ILT in aneurysm stabilization, and the implications of antithrombotic drugs in AAA treatment.

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          Most cited references85

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          Angiotensin II promotes atherosclerotic lesions and aneurysms in apolipoprotein E-deficient mice.

          Increased plasma concentrations of angiotension II (Ang II) have been implicated in atherogenesis. To examine this relationship directly, we infused Ang II or vehicle for 1 month via osmotic minipumps into mature apoE(-/-) mice. These doses of Ang II did not alter arterial blood pressure, body weight, serum cholesterol concentrations, or distribution of lipoprotein cholesterol. However, Ang II infusions promoted an increased severity of aortic atherosclerotic lesions. These Ang II-induced lesions were predominantly lipid-laden macrophages and lymphocytes; moreover, Ang II promoted a marked increase in the number of macrophages present in the adventitial tissue underlying lesions. Unexpectedly, pronounced abdominal aortic aneurysms were present in apoE(-/-) mice infused with Ang II. Sequential sectioning of aneurysmal abdominal aorta revealed two major characteristics: an intact artery that is surrounded by a large remodeled adventitia, and a medial break with pronounced dilation and more modestly remodeled adventitial tissue. Although no atherosclerotic lesions were visible at the medial break point, the presence of hyperlipidemia was required because infusions of Ang II into apoE(+/+) mice failed to generate aneurysms. These results demonstrate that increased plasma concentrations of Ang II have profound and rapid effects on vascular pathology when combined with hyperlipidemia, in the absence of hemodynamic influences.
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            Abdominal aortic aneurysm.

            Abdominal aortic aneurysms cause 1.3% of all deaths among men aged 65-85 years in developed countries. These aneurysms are typically asymptomatic until the catastrophic event of rupture. Repair of large or symptomatic aneurysms by open surgery or endovascular repair is recommended, whereas repair of small abdominal aortic aneurysms does not provide a significant benefit. Abdominal aortic aneurysm is linked to the degradation of the elastic media of the atheromatous aorta. An inflammatory cell infiltrate, neovascularisation, and production and activation of various proteases and cytokines contribute to the development of this disorder, although the underlying mechanisms are unknown. In this Seminar, we aim to provide an updated review of the pathophysiology, current and new diagnostic procedures, assessment, and treatment of abdominal aortic aneurysm to provide family practitioners with a working knowledge of this disorder.
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              Is Open Access

              Platelet secretion: From haemostasis to wound healing and beyond

              Upon activation, platelets secrete more than 300 active substances from their intracellular granules. Platelet dense granule components, such as ADP and polyphosphates, contribute to haemostasis and coagulation, but also play a role in cancer metastasis. α-Granules contain multiple cytokines, mitogens, pro- and anti-inflammatory factors and other bioactive molecules that are essential regulators in the complex microenvironment of the growing thrombus but also contribute to a number of disease processes. Our understanding of the molecular mechanisms of secretion and the genetic regulation of granule biogenesis still remains incomplete. In this review we summarise our current understanding of the roles of platelet secretion in health and disease, and discuss some of the hypotheses that may explain how platelets may control the release of its many secreted components in a context-specific manner, to allow platelets to play multiple roles in health and disease.
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                Author and article information

                Journal
                Blood
                American Society of Hematology
                0006-4971
                1528-0020
                December 20 2018
                December 20 2018
                : 132
                : 25
                : 2619-2628
                Affiliations
                [1 ]Department of Medicine (Cardiology) and
                [2 ]Department of Surgery (Cardiac Surgery), University of Rochester School of Medicine, Rochester, NY; and
                [3 ]Division of Cardiovascular Health and Disease and
                [4 ]Pathobiology and Molecular Medicine, Department of Internal Medicine, The University of Cincinnati College of Medicine, Cincinnati, OH
                Article
                10.1182/blood-2017-08-743237
                6302498
                30228233
                5875eaf4-be0d-48f5-9369-f83e11809d66
                © 2018
                History

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