Differential expression of coxsackievirus and adenovirus receptor in endomyocardial tissue of patients with myocarditis

Abstract

Recent studies demonstrated that the expression of coxsackievirus and adenovirus receptor (CAR) is implicated in the pathophysiology of myocarditis. The aim of the present study was to assess the association between active and borderline myocarditis and CAR expression in endomyocardial tissues, and analyze the association between CAR expression and treatment response. An analytic, cross-sectional, retrospective study was performed in 26 patients with myocarditis and 10 control subjects without heart disease. Myocardial biopsies were obtained and CAR transcription was measured by reverse transcription-quantitative polymerase chain reaction analysis. The association between CAR mRNA levels and the response to immunosuppressive or conventional therapy (treatment responders, n=17; non-responders, n=9) or with the type of histological myocarditis (active myocarditis, n=16; borderline myocarditis, n=10) was analyzed. CAR transcription levels were significantly lower (P=0.012) in patients with myocarditis compared with controls, and a significant decrease was observed (P=0.023) in CAR mRNA levels among patients with borderline myocarditis compared with the no myocarditis group. Patients responding to therapy exhibited higher CAR mRNA levels (P=0.036) compared with patients not responding to treatment, as evaluated based on clinical and echocardiographic criteria (immunosuppressive therapy, n=8; conventional therapy, n=1). Myocarditis in non-responders was associated with fewer clinical manifestations and lower CAR mRNA levels. A significant difference was only found regarding the use of oral steroids in patients with active myocarditis who responded to treatment (P=0.02), with no difference in borderline myocarditis. In conclusion, the transcriptional level of CAR is low in the endomyocardial tissue of patients with myocarditis, and it is lower in borderline myocarditis and in non-responder patients. These findings may enable early identification of patients who may benefit from treatment and timely determination of prognosis.

Human Coxsackie- and adenovirus receptor is a putative target of neutrophil elastase-mediated shedding

“…Therefore, CAR shedding by neutrophil proteases might be a regulatory mechanism of the immune reaction. Furthermore, cardiomyocyte-specific CAR knockdown in adult mice resulted in AV-block [41,42] and low CAR levels were associated with arrhythmia vulnerability, cardiac conduction failure, and failed recovery from infarction in patients [43][44][45][46]. Besides, CAR may act as a pathfinder protein after cardiac injury as increased CAR levels were described in a rat infarction model [47] and in patients suffering from myocarditis and dilated cardiomyopathy [46,48].…”

CXADR: From an Essential Structural Component to a Vital Signaling Mediator in Spermatogenesis

“…In addition, low CXADR expression levels are found to be associated with arrhythmia vulnerability and cardiac conduction failure. Patients with low levels of CXADR also encounter difficulty in recovery from cardiomyopathy [ 29 , 55 , 56 , 57 ]. Cardiac CXADR expression levels seem to be a crucial factor in determining the functionality of cardiomyocytes.…”

Toll-Like Receptors: Are They Taking a Toll on the Heart in Viral Myocarditis?

“…CAR was found to be upregulated in the myocardium of explanted DCM hearts compared to hearts of patients with other cardiac diseases or healthy donors [68,88,89]. However, it has become evident that CAR upregulation is not limited to inflammatory cardiomyopathy or DCM, but also occurs in cardiac pathology unrelated to myocarditis [90][91][92][93]. As CAR has a significant role in foetal cardiac development, upregulation might have importance in the regeneration of damaged myocardium [90,94].…”