Abstract

Cardiovascular diseases and aging induce stress on the heart, resulting in heart wall thickness and stiffness associated with increased fibrosis. The sinoatrial node (SAN) is the heart’s natural pacemaker composed of a fibrous tissue matrix with a heterogenous cellular population. With aging, activated fibroblasts can create scar tissue, thus commonly resulting in sick sinus syndrome (SSS) and arrhythmias. SSS is produced by idiopathic degeneration of the SAN, requiring implantation of electronic pacemakers. Phototherapy or photobiomodulation (PBM) is a technique with many therapeutic properties that has been applied clinically to treat various forms of tissue pathology. Although there has been evidence that PBM has positive effects on the heart to improve cardiac function and prevent infarction, its age associated changes during wound healing are unknown. This study uses timelapse microscopy and red light (630 nm) or near-infrared (NIR, 810 nm) PBM on SAN support cells (SANspc) isolated from 2 months (2mo) and 2 years (2y) old mice during in vitro wound healing. With an average initial gap width of 540 μm, the kinetics and extent of wound closure are measured for each of the SANspc age and treatment groups. Nonirradiated SANspc served as controls. Aging slowed kinetics and increased the extent of wound healing by an average of 1.87 hours earlier than that of the 2mo-SANspc (p < 0.05). Irradiation with red light induces a significantly faster scale of closure for the gap width to close between ½ and ¾ by 0.25 and 0.68 hours, in 2mo- and 2y-SANspc respectively, compared to their corresponding age control. With red irradiation, 2y-SANspc resulted in a significantly faster scale of closure of 0.52 hours compared to 2mo-SANspc. Irradiation with NIR resulted in the opposite effect in both age groups, in which the scale of closure for the wound slowed significantly (0.19 and 0.71 hours in the 2mo- and 2y-SANspc, respectively). In conclusion, these data suggests that SANspc migration and proliferation capacity is faster with aging and red irradiation increases wound closing effect in both age groups. Thus, the enhanced wound healing induced by PBM may be an attractive therapeutic approach to target cardiac fibrosis and promote cardiac remodeling in the aging heart.

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