Resident Wake Forest Hospital Winston-Salem, North Carolina, United States
Disclosure(s):
Sidish Venkataraman, MD: No financial relationships to disclose
Introduction: Spontaneous intracerebral hemorrhage (ICH) is a devastating sub-type of stroke. Nearly 60% of spontaneous ICH is due to HTN. Recent studies have suggested that the body’s inflammatory response to ICH may be primarily driven by pro-inflammatory macrophages modified by the PIEZO 1 mechanoreceptor. To date, however, there have been few advances in the treatment of this crippling disease. One barrier to translating laboratory findings into clinical therapeutics has been the lack of an animal model that mirrors HTN and metabolic syndrome, the comorbidities seen in the patient population that most often suffers from spontaneous ICH
Methods: Our lab has been working with the hypertensive Ren-2 transgenic rat (mREN-2)27 model to mimic HTN and metabolic syndrome. Our previous research has demonstrated significantly higher levels of serum IL-12, a pro-inflammatory cytokine, in the mREN model as compared to Sprague Dawley (SD) controls, consistent with human data. We hypothesize that HTN worsens secondary brain injury following spontaneous ICH via PIEZO1 by inducing macrophages to release IL-12 leading to a pro-inflammatory state and impeding inflammation resolution and hematoma resorption. We are currently testing this hypothesis by harvesting bone marrow derived and circulating macrophages from mREN and SD rats, culturing the macrophage cell lines, treating the cells with the PIEZO1 agonist, YODA1, and antagonist, GsMTX-4, and then measuring IL-12 release.
Results: Our initial data indicates that both mREN and SD rats have similar levels of PIEZO1 expression in bone marrow derived macrophage cells suggesting that differences in PIEZO1 are not due to inherent or transgenic differences but are rather HTN induced. Our next steps will be to quantify cytokine release following treatment of rat macrophage cells with PIEZO1 agonist/antagonists.
Conclusion : We hope that by establishing a link between PIEZO and macrophage IL-12 release we may provide additional therapeutic targets for ICH resolution in patients with spontaneous ICH.
