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Mapping Platelet Responses in Native American Populations
Author(s) -
Stein Sarah J.,
Rodezno Tania G.,
Graber Katelyn N.,
Hora Kirby A.,
Clarke Santa M.,
Pahlke Rachel S.,
Abbott Karla M.,
Larson Mark K.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.572.4
Subject(s) - platelet , platelet activation , receptor , thrombin receptor , hemostasis , von willebrand factor , medicine , thrombin , integrin , adenosine diphosphate , thromboxane a2 , pharmacology , endocrinology , immunology , platelet aggregation
Platelets, key cellular components in normal hemostasis, can contribute to cardiovascular disease progression and are altered by certain drug therapies. These effects occur via a wide array of protein receptors that can respond to various in vivo signals and pharmaceutical products. Research has shown that the degree of platelet reactivity to either cellular signals or drugs may vary widely among individuals based upon the presence of receptor allele polymorphisms enriched within certain ethnicities. For example, African American populations have a variant in the thrombin receptor PAR‐4 that results in greater degrees of platelet activation and refractivity towards anti‐platelet medications compared to Caucasian populations (Edelstein et al., 2014, Blood 124: 3450–3458). As such, we novelly compared Caucasian and Native American populations by mapping platelet responses to five agonists that target distinct platelet receptors. Twenty‐five Native American subjects were studied along with age and sex‐matched Caucasian subjects. Flow cytometric analysis of platelet GPIIb/IIIa integrin conformational activation was used to measure the dose‐response effects of agonists on platelet activation, and SPSS was used to perform statistical analyses. Results showed that Native American subjects displayed higher levels of activation in response to lower doses of adenosine diphosphate (ADP) and thrombin receptor activating peptide (TRAP) compared to Caucasian subjects. However, no activation profile differences were observed following agonism of collagen, thromboxane, or von Willebrand factor receptors. This implies that medications targeting ADP and/or thrombin receptors could have varying responses in patients, or that those medications may not be optimal when treating patients with these receptor‐response variances. The data provide insight into possible platelet receptor variants between Native Americans and Caucasians that warrants further investigation. Support or Funding Information Research was supported in part by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health (P20GM103443), as well as funding from the National Science Foundation/EPSCoR program [IIA‐1355423], the state of South Dakota, and an undergraduate fellowship from the American Physiological Society. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .