Abstract 16522: Immunosenescence-Associated MicroRNAs in Age and Heart Failure
Increasing age is a major risk factor for cardiovascular diseases and is associated with a decline of organ repair capacity. Aging of the immune system, immunosenescence, is characterized by an impairment of lymphopoiesis, especially B-lymphocyte maturation, and is a hallmark of chronic heart failure (CHF). MicroRNAs (miRs) are non-coding, small RNAs, which post-transcriptionally control gene expression of multiple target genes. The miR-181 family was shown to be involved in B-lymphopoiesis and recent reports revealed an inhibitory effect of high levels of miR-34a on B-cell maturation. We studied the role of these miRs in immunosenescence and changes in the immune system related to CHF. We conducted a clinical study analyzing total peripheral blood (PB) cells of young healthy controls (young-HC; 25±4years; n=14), old healthy controls (old-HC; 64±6years; n=6) and age-matched elderly patients with chronic heart failure (CHF 65±11years; n=14). Consistent with previous reports, we found higher counts of leukocytes and reduced lymphocyte counts, especially T-cytotoxic cells (-1.8-fold; p=0.01) and B-cells (1.6-fold; p<0.01) as well as increased monocyte and neutrophil counts in aged individuals and even more pronounced changes in in CHF patients. The expression of miR-181 family members in PB was reduced by increasing age and CHF. Particularly, miR-181c levels were significantly reduced in old-HC and were further reduced in CHF patients (young vs. old-HCs: -2-fold, p<0.01, correlation with age: r=-0.5; p<0.01). The expression levels of miR-181c correlate with the overall number of B-cells (r=0.4; p<0.01) and with the number of naïve B-cells (r=0.4; p<0.01). In contrast, miR-34a expression levels were increased in old-HCs compared to young-HCs (1.9-fold, p=0.04; correlation with age: r=0.54; p=0.01). In summary, aging- and CHF-associated changes in PB leukocyte subsets are paralleled by alterations in the expression of miRs involved in lymphopoiesis, which might play a key role in the age-related and CHF-mediated dysregulation of immune functions resulting in immunosenescence.
- © 2011 by American Heart Association, Inc.