Matthew B Murphy, Zhenjiang Yang, Tuerdi Subati, Eric Farber-Eger, Kyungsoo Kim, Daniel J Blackwell, Matthew R Fleming, Joshua M Stark, Joseph C Van Amburg, Kaylen K Woodall, Justin P Van Beusecum, Vineet Agrawal, Charles D Smart, Ashley Pitzer, James B Atkinson, Agnes B Fogo, Julie A Bastarache, Annet Kirabo, Quinn S Wells, Meena S Madhur, Joey V Barnett, Katherine T Murray
AIMS: The lymphocyte adaptor protein (LNK) is a negative regulator of cytokine and growth factor signaling. The rs3184504 variant in SH2B3 reduces LNK function and is linked to cardiovascular, inflammatory, and hematologic disorders including stroke. In mice, deletion of Lnk causes inflammation and oxidative stress. We hypothesized that Lnk-/- mice are susceptible to atrial fibrillation (AF) and that rs3184504 is associated with AF and AF-related stroke in humans. During inflammation, reactive lipid dicarbonyls are a major component of oxidative injury, and we further hypothesized that these mediators are critical drivers of the AF substrate in Lnk-/- mice...
February 20, 2024: Cardiovascular Research