Activation of T Lymphocytes as a Novel Mechanism in Beta1-Adrenergic Receptor Autoantibody-Induced Cardiac Remodeling

• Background: Numerous studies have reported significantly elevated titers of serum autoantibody against the second extracellular loop of β 1 -adrenoceptor (β 1 -AA), a catecholamine-like substance with β 1 -adrenergic activity, in patients with heart failure. Although evidence demonstrates that this autoantibody may alter T cell proliferation and secretion, the role of T lymphocytes in heart failure induced by β 1 -AA remains unclear. The current study was designed to determine whether T cell disorder contributes to heart failure induced by β 1 -AA. Methods and Results: β 1 -AA monoclonal antibodies (β 1 -AAmAb) produced using the hybridoma technique were administered in wild-type mice or T lymphocyte deficiency nudes for 12weeks. T lymphocytes from heart failure patients and neonatal cardiomyocytes were utilized in vitro. Mouse protein antibody array analysis was employed to detect the cytokines responsible for β 1 -AAmAb-induced heart failure. Compared to wild-type mice, T lymphocyte deficiency mice prevented cardiac function from getting worse, attenuated adverse remodeling, and ameliorated cardiomyocyte apoptosis and fibrosis. As shown by protein array, the serum level of interleukin (IL)-6 was significantly lower in the nude group as compared to wild-type after β 1 -AAmAb treatment. Mechanistic studies in vitro demonstrated that T lymphocyte culture supernatants stimulated by β 1 -AAmAb caused direct damage in the cardiomyocytes, and β 1 -AAmAb promoted proliferation of T lymphocytes isolated from patients with heart failure and increased IL-6 release. IL-6-specific siRNA virtually abolished cardiomyocyte apoptosis, suggesting that IL-6 may be a key cytokine released by T lymphocytes and responsible for β 1 -AAmAb-induced cardiac remodeling. Conclusions: Collectively, we demonstrate that β 1 -AAmAb-induced cardiac remodeling via mediating T lymphocyte disorder and releasing a variety of IL-6. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Kardiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)

Keyword

Autoantibody

Beta-1

Receptors adrenergic

Remodeling

T lymphocytes

Publication and Content Type

ref (subject category)

art (subject category)