The role of platelets in the initial stages of atherosclerosis

Jørgensen, Leif

doi:10.1111/j.1538-7836.2006.02006.x

Cited by 31 publications

(23 citation statements)

References 29 publications

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“…18,19 Since then, results of numerous studies support fibrin formation as integral in the developing atherogenic process. [20][21][22][23][24][25][26][27][28][29][30] While the exact sequence of events that leads to plaque formation continues to be debated, there is more uniform agreement about fibrin deposition during the course of plaque growth, rupture, and acute thrombotic complications. Procoagulant processes that culminate in fibrin formation have been exhaustively studied, with elevations of selected clotting factor proteins or their activities considered as risk factors for atherogenesis or its acute complications.…”

mentioning

confidence: 99%

The effect of a single nucleotide polymorphism on human α2-antiplasmin activity

Christiansen

Jackson

Lee

et al. 2007

Blood

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The primary inhibitor of plasmin, 2-antiplasmin (2 AP), is secreted by the liver into plasma with Met as the amino-terminus. During circulation, Met-2 AP is cleaved by antiplasmin-cleaving enzyme (APCE), yielding Asn-2 AP, which is crosslinked into fibrin approximately 13 times faster than Met-2 AP. The Met-2 AP gene codes for either Arg or Trp as the sixth amino acid, with both polymorphic forms found in human plasma samples. We determined the Arg6Trp genotype frequency in a healthy population and its effects on Met-2 AP cleavage and fibrino-lysis. Genotype frequencies were RR 62.5%, RW 34.0%, and WW 3.5%. The polymorphism related to the percentage of Met-2 AP in plasma was WW (56.4%), RW (40.6%), and RR (23.6%). WW plasma tended to have shorter lysis times than RR and RW plasmas. APCE cleaved purified Met-2 AP(Arg6) approximately 8-fold faster than Met-2 AP(Trp6), which is reflected in Asn-2 AP/Met-2 AP ratios with time in RR, RW, and WW plasmas. Removal of APCE from plasma abrogated cleavage of Met-2 AP. We conclude that the Arg6Trp polymorphism is functionally significant, as it clearly affects conversion of Met-2 AP to Asn-2 AP, and thereby, the rate of 2 AP incorporation into fibrin. Therefore, the Arg6Trp poly-morphism may play a significant role in governing the long-term deposition/re-moval of intravascular fibrin. (Blood. 2007; 109:5286-5292)

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confidence: 99%

The effect of a single nucleotide polymorphism on human α2-antiplasmin activity

Christiansen

Jackson

Lee

et al. 2007

Blood

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“…Notwithstanding, animals employed in these long-period studies tend to be within the prepuberty period, and in consequence their lesions are not as severe as those developed in adult humans over the years. Older animals (over 6 months) can be used to obtain atherosclerotic models of higher human resemblance [50], but management becomes more difficult because of their considerable weight (up to 150 kg). To overcome size-related problems, the minipigs are becoming increasingly used.…”

Section: The Pig As a Tool For Atherothrombotic Diseasementioning

confidence: 99%

Atherosclerosis and Thrombosis: Insights from Large Animal Models

Vilahur

Padró

Badimon

2011

BioMed Research International

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Atherosclerosis and its thrombotic complications are responsible for remarkably high numbers of deaths. The combination of in vitro, ex vivo, and in vivo experimental approaches has largely contributed to a better understanding of the mechanisms underlying the atherothrombotic process. Indeed, different animal models have been implemented in atherosclerosis and thrombosis research in order to provide new insights into the mechanisms that have already been outlined in isolated cells and protein studies. Yet, although no model completely mimics the human pathology, large animal models have demonstrated better suitability for translation to humans. Indeed, direct translation from mice to humans should be taken with caution because of the well-reported species-related differences. This paper provides an overview of the available atherothrombotic-like animal models, with a particular focus on large animal models of thrombosis and atherosclerosis, and examines their applicability for translational research purposes as well as highlights species-related differences with humans.

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“…Platelet activation is a central precursor to thrombus formation, which in turn can provoke cardiac ischemia and consequent acute coronary syndromes (Camacho and Dimsdale 2000;von Känel et al 2001;Yip et al 2005;Croce and Libby 2007). Moreover, activated platelets can accelerate atherosclerosis development by facilitating leukocyte migration into the vascular endothelium (Hu et al 2003;Jorgensen 2006;Brydon et al 2006). In particular, two markers of platelet activation may be particularly relevant to these disease processes:…”

Section: Introductionmentioning

confidence: 98%

Longitudinal platelet reactivity to acute psychological stress among older men and women

Aschbacher

Känel

Mills

et al. 2009

Stress

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Platelet reactivity to acute stress is associated with increased cardiovascular disease risk; however, little research exists to provide systematic methodological foundations needed to generate strong longitudinal research designs. Study objectives were: 1) to evaluate whether markers of platelet function increase in response to an acute psychological stress test among older adults, 2) to establish whether reactivity remains robust upon repeated administration (i.e. three occasions approximately 1 year apart), and 3) to evaluate whether two different acute speech stress tasks elicit similar platelet responses. The 149 subjects (mean age 71 years) gave a brief impromptu speech on one of two randomly assigned topics involving interpersonal conflict. Blood samples drawn at baseline and post-speech were assayed using flow cytometry for platelet responses on three outcomes (% aggregates, % P-selectin expression, and % fibrinogen receptor expression). Three-level hierarchical linear modeling analyses revealed significant stress-induced increases in platelet activation on all outcomes ( p , 0.001). No significant habituation on any measure was found. Additional reactivity differences were associated with male gender, history of myocardial infarction, and use of aspirin, statins, and antidepressants. The results demonstrate that laboratory acute stress tests continued to produce robust platelet reactivity on three activation markers among older adults over 3 years.

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The role of platelets in the initial stages of atherosclerosis

Cited by 31 publications

References 29 publications

The effect of a single nucleotide polymorphism on human α2-antiplasmin activity

The effect of a single nucleotide polymorphism on human α2-antiplasmin activity

Atherosclerosis and Thrombosis: Insights from Large Animal Models

Longitudinal platelet reactivity to acute psychological stress among older men and women

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