Background: Myocardial infarction (MI) remains an important cause of morbidity and mortality. Ischemic injury during MI produces impairment of left ventricular (LV) function. The MI induces elevation of JNK/ERK ratio which in turn controls nuclear factor of activated T cells (NFAT). Lower JNK leads to reduced cardiomyocyte death. ERK activation induces a prominent cardiac mechanosensor Syndecan-4 (Syn4) cardioprotective signaling pathway. Syn4 dependent regulation of the JNK/ERK profoundly effects cardiomyocyte survival and elevated NFAT contributes to compromised LV morphology and function after MI. Increased NFAT was linked to reduction in LV Syn4. Vibroacoustic Transthoracic Stimulation (VATS) is the noninvasive sonic stimulation via a wearable chest harness. VATS induces pulsatile shear stress on the left ventricle (LV) via penetrating rhythmic sound waves. We have previously reported that Syn4 was elevated in response to VATS after MI and may induce cardioprotection. Objective: We hypothesize that VATS may induce Syn4 mechanosensor cardioprotective control of NFAT and JNK/ERK.
Methods: After MI, rats (SD-300gms) were treated by 1hr/day VATS (MI-VATS) (n=5) or no treatment - Control (MI) (n=5) for 4 weeks. LV fibrosis and levels of NFAT, JNK, ERK, Syn4 proteins after MI with or without VATS were analyzed.
Results: JNK/ERK ratio and NFAT levels were lower in LV of MI-VATS rats by 63% and 30% respectively when compared to MI (p<0.01). LV fibrosis was reduced by 19% (p<0.01). VATS significantly increased Syn4 and LV function (p<0.01, MI vs MI-VATS)
Conclusions: Our findings suggest that after MI VATS noninvasively improves LV morphology and function via mechanosensor modulation of NFAT, JNK and ERK, possibly via transcriptional mechanism. Noninvasive vibroacoustic downregulation of the NFAT-Jun pathways may be useful for cardiac rehabilitation.