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Whole Genome RNAseq Studies of Blood in Smokers vs Nonsmoke

Institution: University of California, Davis
Investigator(s): Frank Sharp, M.D.
Award Cycle: 2018 (Cycle 27) Grant #: 27IP-0011 Award: $400,000
Subject Area: Cardiovascular and Cerebrovascular Disease
Award Type: High Impact Pilot Award

Initial Award Abstract

Smoking can increase the risk of both ischemic stroke (IS) and intracerebral hemorrhage (ICH). This is a paradox since ischemic stroke occurs because of embolized clots or clotting in situ, whereas intracerebral hemorrhage (ICH) occurs because of rupture of a blood vessel and bleeding into the brain parenchyma. The factors from smoking that can cause clotting in some individuals with ischemic stroke and cause bleeding in some individuals with intracerebral hemorrhage are not known. This study will begin to unravel this mystery by taking blood samples from patients with IS and ICH and compare smokers to nonsmokers. The blood samples are processed for RNA sequencing, a procedure that makes it possible to measure the RNA levels of every known gene in the blood. We can then compare the regulated genes in smokers versus nonsmokers for both IS and ICH. We expect to find that in those patients who smoke and who have IS they will have upregulation of genes that predispose to clotting and inflammation. In contrast, we expect to find in those patients who smoke and who have ICH they will have upregulation of genes that predispose to disruption of their blood vessels and predispose to bleeding. The data to be obtained for IS and ICH should help in understanding the basic mechanisms of how smoking contributes to clotting in some patients and to bleeding in others. Of more practical benefit the data could also be used to guide preventive treatment in that patients predisposed to clotting and IS could be treated with anti-platelet agents or one of the new safe anticoagulants, whereas those patients predisposed to ICH should avoid these agents.