Low density lipoprotein receptor-related protein 1 regulates cardiac hypertrophy induced by pressure overload.
Int J Cardiol
; 299: 235-242, 2020 01 15.
Article
en En
| MEDLINE
| ID: mdl-31350035
ABSTRACT
BACKGROUND:
Cardiac hypertrophy is associated with functional changes in cardiomyocytes, which often results in heart failure. The low-density lipoprotein receptor-related protein 1 (LRP1) is a large multifunctional endocytic receptor involved in many physiological and pathological processes. However, its function in the development of cardiac hypertrophy remains largely unclear.METHODS:
Adenoviral constructs were used for either overexpression or silencing of LRP1 in both in vitro and in vivo experiments. Cardiac function was measured using the Millar catheter.RESULTS:
LRP1 expression was upregulated in both transverse aortic constriction (TAC)-induced hypertrophic myocardium and catecholamine (phenylephrine (PE) and norepinephrine (NE))- and angiotensin II (AngII)-induced hypertrophic cardiomyocytes. In addition, cell surface area, protein/DNA ratio, and the mRNA levels of hypertrophic markers were significantly increased in LRP1-overexpressing cardiomyocytes without catecholamine stimulation. Conversely, LRP1 inhibition by LRP1-specific siRNA or a specific ligand-binding antagonist (RAP) significantly rescued hypertrophic effects in PE, NE, or AngII-induced cardiomyocytes. LRP1 overexpression induced PKCα, then activated ERK, resulting in cardiac hypertrophy with the downregulation of SERCA2a and calcium accumulation, which was successfully restored in both LRP1-silenced cardiomyocytes and TAC-induced hearts.CONCLUSIONS:
LRP1 regulates cardiac hypertrophy via the PKCα-ERK dependent signaling pathway resulting in the alteration of intracellular calcium levels, demonstrating that LRP1 might be a potential therapeutic target for cardiac hypertrophy.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Cardiomegalia
/
Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad
/
Miocitos Cardíacos
Límite:
Animals
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Humans
/
Male
Idioma:
En
Revista:
Int J Cardiol
Año:
2020
Tipo del documento:
Article