Low‐intensity pulsed ultrasound attenuates cardiac inflammation of CVB3‐induced viral myocarditis via regulation of caveolin‐1 and MAPK pathways

Abstract

The aggressive immunological activity elicited by acute viral myocarditis contributes to a large amount of cardiomyocytes loss and poor prognosis of patients in clinic. Low‐intensity pulsed ultrasound ( LIPUS ), which is an effective treatment modality for osteoarthropathy, has been recently illustrated regulating the overactive inflammatory response in various diseases. Here, we aimed to investigate whether LIPUS could attenuate coxsackievirus B3 ( CVB 3) infection‐induced injury by coordinating the inflammatory response. Male BALB /c mice were inoculated intraperitoneally with CVB 3 to establish the model of acute viral myocarditis. LIPUS treatment was given on Day 1, Day 1, 3 and Day 1, 3, 5 post‐inoculation, respectively. All mice were followed up for 14 days. Day 1, 3, 5 LIPUS treatment significantly improved the survival rate, attenuated the ventricular dysfunction and ameliorated the cardiac histopathological injury of CVB 3‐infected mice. Western blotting analysis showed Day 1, 3, 5 LIPUS treatment decreased pro‐inflammatory cytokines, increased the activation of caveolin‐1 and suppressed p38 mitogen‐activated protein kinase ( MAPK ) and extracellular signal‐regulated kinase ( ERK ) signallings in heart tissue. RAW 264.7 cells were treated with lipopolysaccharides ( LPS ) to simulate the augmented inflammatory response in vivo. LIPUS treatment on RAW264.7 inhibited the expression of pro‐inflammatory cytokines, activated caveolin‐1 and suppressed p38 MAPK and ERK signallings. Transfecting RAW 264.7 with caveolin‐1 si RNA blunted the suppression of pro‐inflammatory cytokines and MAPK signallings by LIPUS treatment. Taken together, we demonstrated for the first time that LIPUS treatment attenuated the aggressive inflammatory response during acute viral myocarditis. The underlying mechanism may be activating caveolin‐1 and suppressing MAPK signallings.

Ultrasound Therapy: Experiences and Perspectives for Regenerative Medicine

“…LIPUS has been recently reported to have biologic relevance in the context of inflammation. LIPUS treatment was shown to alleviate the lipopolysaccharide-induced inflammatory response in murine RAW264.7 macrophages by increasing the activation of caveolin-1 [ 95 ], and also improved the general status of coxsackievirus-B3-infected mice including their ventricular function by suppressing CD68+ infiltration in the heart [ 96 , 97 ]. Related to inflammation, LIPUS was found to inhibit the inflammatory pathways activated during aseptic joint loosening [ 97 ], suggesting an anti-inflammatory role for LIPUS in the orthopedic context.…”

Inhaled gold nanoparticles cause cerebral edema and upregulate endothelial aquaporin 1 expression, involving caveolin 1 dependent repression of extracellular regulated protein kinase activity

“…Another report indicated that the protein interaction of Cav1 and kinase suppressor of Ras 1 (KSR1) is essential for ERK activation in mouse embryo fibroblasts (MEFs), and the disruption of Cav1- KSR1 interaction by KSR1 mutant evidently abolished ERK activation [45] . These data report Cav1 to be a positive regulator of ERK signaling in astrocytes and MEFs [46], however, lots of studies report the relationship between ERK activity and Cav1 exhibit reciprocally negative action in endothelial cells and macrophages [47, 48] . Connexin 43 inhibition in cultured HUVECs decreased the phosphorylation of ERK but increased the expression of Cav1.…”

Low‐intensity Pulsed Ultrasound Ameliorates Angiotension Ii-induced Cardiac Fibrosisbyalleviating Inflammation via a Caveolin-1-dependent Pathway

“…LIPUS, a novel ultrasonic therapy technique, has been shown to exert its biological effects in fracture healing and tumor treatment without tissue compression, overheating, and other side effects ( [45,46]). Recently, LIPUS irradiation has been reported to suppress myocardial brosis induced by acute MI in animal models ( [17]). Therefore, further investigations were performed to con rm whether LIPUS irradiation could ameliorate AngII-induced cardiac hypertrophy and brosis.…”

“…In addition to the diagnostic role of ultrasound, low-intensity pulsed ultrasound (LIPUS), a safe and noninvasive method of mechanical stimulation, has been studied and widely applied to treat various diseases clinically through regulating in ammatory responses and downstream intracellular signaling pathways ( [13][14][15][16][17]). Previous studies have revealed that LIPUS therapy could attenuate and reverse cardiac dysfunction and ameliorate myocardial brosis in animal models of myocardial infarction (MI) and transverse aortic constriction (TAC) through the involvement of mechanotransduction and activation of the p38 MAPK signaling pathways ( [18][19][20]).…”