TABLE 2.

Differentially regulated genes with acute (2 day) exercise of the ECM-receptor, integrin, and cell-cell communication pathways associated with hypertrophic remodeling and/or atrial fibrillation (AF).

Gene	Gene product	Directional change with swim exercise	Tumor necrosis factor (TNF) dependent?	Link(s) to fibrotic and/or hypertrophic remodeling and atrial fibrillation
Ccnd3	Cyclin D3	↓	No	A protein shown to be upregulated during hypertrophic growth (Busk et al., 2002) and linked to the pathogenesis of AF (Li et al., 2019)
Elk1	Elk-1	↓	No	A transcription factor that is phosphorylated via MEK/ERK kinases and plays a role in cardiac hypertrophy (Babu et al., 2000) as well as regulating stretch-mediated atrial natriuretic factor (ANF) expression (Mahida, 2013)
Fgf2	Fibroblast growth factor 2	↑	Yes	A multifunctional polypeptide that is upregulated by stress (Kardami et al., 2004) and involved in p38 MAPK-mediated cardiac hypertrophy (Tanaka et al., 1999) as well as fibrosis (Itoh and Ohta, 2013)
Gsk3β	Glycogen synthase kinase 3 beta	↑	Yes	An enzyme that serves as a hub for the regulation of both physiological and pathological hypertrophic and fibrotic remodeling (Lal et al., 2015) via TNF-related pathways (Sugden et al., 2008)
Itga1	Integrin, alpha 1	↑	Yes	Cell-cell and cell-matrix adhesion (ECM-receptor interactions), upregulated in AF and linked to rhythm outcome of AF catheter ablation (Husser et al., 2016)
Lama5	Laminin subunit alpha-5	↑	Yes	A component of the ECM, specifically basement membranes, that is upregulated in AF (Husser et al., 2016)
Mmp13	Matrix metalloproteinase 13	↓	Yes	A matrix metalloproteinase and collagenase that targets collagens I and III and is linked to cardiac hypertrophy and fibrosis in pressure overload hearts (Spinale, 2002)
Plod2	Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2)	↓	No	Lysyl hydroxylase linked to both TNF- and TGFβ1-mediated pyridinoline cross-linking inherent to fibrotic cardiac remodeling (van der Slot et al., 2005)
Tln1	Talin-1	↑	Yes	A protein mediating cell-cell adhesion linked to AF (Weeke et al., 2014) and becomes more prominent at costameres during mechanical stress and modulates hypertrophic and fibrotic remodeling (Manso et al., 2013)