Data from our lab and others demonstrate that there is greater cardiac T cell infiltration with age and that these T cells play a role in pathogenic cardiac hypertrophy and fibrosis. However, how T cells are recruited to the heart with advanced age is unknown. PURPOSE: The purpose of this study was to assess age-related alterations in T cell recruiting chemokine and chemokine receptor gene expression in the heart. METHODS: This study was conducted using five young (4-6 months old) and five old (22-24 months old) mice. Following euthanasia, the heart tissue was snap frozen and homogenized. RNA was extracted using the phenol/chloroform method. Following cDNA synthesis, qPCR was performed for the chemokines Ccl2, Ccl5, Cxcl10; as well as the 18s gene which was used as an endogenous control. Additionally, we performed qPCR for chemokine receptors, specifically Ccr1, Ccr3, Ccr5, and Cxcr3. After qPCR, relative gene expression was determined using the delta delta CT method. Differences were assessed using an independent sample T test. All data are expressed as mean relative gene expression ± standard error. RESULTS: For the Cxcl10 cytokine, the relative gene expression was 1.43 ± 0.39 in young mice and 3.07 ± 0.52 in old mice (p=0.018). For the chemokine Ccl5, the relative gene expression was 1.03 ± 0.25 in young mice and 7.35 ± 4.37 in old mice (p=0.093). Additionally, the Ccl2 chemokine had a relative gene expression of 1.19 ± 0.47 in young mice and 1.44 ± 0.27 in old mice (p=0.328). Because we observed age related elevations in the Cxcl10 and Ccl5 chemokines, we assessed gene expression for the corresponding chemokine receptors. Ccl5 receptors, Ccr1 (1.73 ± 0.65, young vs. 2.89 ± 0.75, old p=0.140), Ccr3 (1.89 ± 0.73, young vs. 7.19 ± 4.74, old p=0.150), and Ccr5 (1.11± 0.13, young vs. 2.46 ± 0.51, old p=0.017) exhibited trends for elevation. Furthermore, the receptor Cxcr3 which corresponds to the Cxcl10 chemokine had a relative gene expression of 1.26 ± 0.28 in young mice and 8.73 ± 4.96 in old mice (p=0.086). CONCLUSION: In conclusion, these data suggest that gene expression for both the Ccl5 and Cxcl10 chemokine pathways is upregulated in hearts of the old mice. Further, Ccl5 and Cxcl10 may be responsible for the increased T cell recruitment to the aging heart. These chemokines represent a potential treatment target to preserve cardiovascular health in the elderly.
Siddiq, Zaid and Trott, Daniel W.
"Age Related Alterations in Chemokine and Chemokine Receptor Gene Expression in Mouse Hearts,"
International Journal of Exercise Science: Conference Proceedings: Vol. 2:
12, Article 113.
Available at: https://digitalcommons.wku.edu/ijesab/vol2/iss12/113