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Thrombotic Disorders and Nitric Oxide Insufficiency

  • Chapter
Nitric Oxide and the Cardiovascular System

Part of the book series: Contemporary Cardiology ((CONCARD))

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Abstract

Thrombus formation within a coronary vessel is the precipitating event in myocardial infarction and unstable angina as shown in angiographic (1) and pathologic (2) studies. The angiographic severity of coronary stenoses does not adequately predict sites of subsequent acute coronary syndromes. For this reason, rupture of atheromatous plaque in relatively mildly stenosed vessels and subsequent thrombus formation is believed to underlie the majority of acute coronary syndromes (3,4). Both superficial and intimai injury caused by endothelial denudation and deep intimal injury caused by plaque rupture expose collagen and von Willebrand factor to platelets (4). Platelets then adhere directly to collagen or indirectly via the binding of von Willebrand factor to glycoprotein (GP) Ib/IX and to the matrix. Local platelet activation by tissue factor-mediated thrombin generation or by collagen stimulates further thrombus formation and additional platelet recruitment by supporting cell-surface thrombin formation and releasing adenosine diphosphate (ADP), serotonin, and thromboxane A2 (5). Thrombus forms as platelets aggregate via the binding of bivalent fibrinogen to GPIIb/IIIa. In support of these mechanisms, increased platelet derived thromboxane and prostaglandin metabolites have been detected in patients with acute coronary syndromes (6). The importance of platelet activation in acute coronary syndromes is further supported by the clear clinical benefit of treatment with aspirin for both primary and secondary prevention strategies (7,8). In addition, patients with coronary atherosclerosis have impaired bioactivity of endothelial nitric oxide (NO·), a known vasodilator and inhibitor of platelet function. In this chapter, the role of NO· insufficiency in experimental and clinical thrombotic disorders is explored.

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Authors
  1. Jane E. Freedman
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  2. Joseph Loscalzo
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Editors and Affiliations

  1. Boston University Medical Center, Boston, MA, USA

    Joseph Loscalzo MD, PHD  & Joseph A. Vita MD  & 

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Freedman, J.E., Loscalzo, J. (2000). Thrombotic Disorders and Nitric Oxide Insufficiency. In: Loscalzo, J., Vita, J.A. (eds) Nitric Oxide and the Cardiovascular System. Contemporary Cardiology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-002-5_17

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  • DOI: https://doi.org/10.1007/978-1-59259-002-5_17

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-101-1

  • Online ISBN: 978-1-59259-002-5

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