The HIV protease inhibitor, ritonavir, dysregulates human platelet function in vitro
| Autor: | Sherry L. Spinelli, Shannon G. Loelius, Richard P. Phipps, Neil Blumberg, Katie L. Lannan |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Adult
Blood Platelets Male Platelet Aggregation Thromboxane Inflammation HIV Infections 030204 cardiovascular system & hematology Article 03 medical and health sciences Young Adult 0302 clinical medicine immune system diseases Medicine HIV Protease Inhibitor Humans Protease inhibitor (pharmacology) Platelet 030212 general & internal medicine Platelet activation Prostaglandin E2 Aged Ritonavir business.industry virus diseases Hematology HIV Protease Inhibitors Middle Aged Platelet Activation Cardiovascular Diseases Immunology Female medicine.symptom business medicine.drug |
| Popis: | There are 37 million people globally infected with the Human Immunodeficiency Virus (HIV). People living with HIV can achieve nearly normal lifespans due to the use of antiretroviral drugs (ARVs). However, people living with HIV experience chronic inflammation and increased risk for cardiovascular diseases (CVD) relative to uninfected people. While the cause for this risk is unclear, some ARVs have been associated with CVD, and it is speculated that some ARVs potentiate inflammation in infected individuals. Platelets are a critical link between inflammation and the development and progression of CVD, but the effects of ARVs on platelets are largely understudied. In this study, we examined the effects of ARVs on human platelet function in vitro. Our data show that the ARV ritonavir, a protease inhibitor, severely altered human platelet lipid mediator production (prostaglandin E2 and thromboxane) in both resting and activated platelets. Further characterization revealed that ritonavir altered measures of platelet hemostatic and thrombotic function that included significantly decreased platelet spreading, increased platelet aggregation, and trended toward increased clot strength. These data provide proof-of-principle that ARVs can directly dysregulate human platelets, possibly contributing to inflammation-related comorbidities. These data may provide mechanistic insight into the factors contributing to increased risk of CVD in people living with HIV, and may help guide future development of new HIV agents and ARV regimens that mitigate platelet dysregulation by ARVs. |
| Databáze: | OpenAIRE |
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