RESUMO
Structural dilation of cardiomyocytes (CMs) imposes a decline in cardiac performance that precipitates cardiac failure and sudden death. Since membrane proteins are implicated in dilated cardiomyopathy and heart failure, we evaluated the expression of the sarcolemmal membrane-associated protein (SLMAP) in dilated cardiomyopathy and its effect on CM contraction. We found that all 3 SLMAP isoforms (SLMAP-1, -2, and -3) are expressed in CMs and are downregulated in human dilated ventricles. Knockdown of SLMAPs in cultured CMs transduced with recombinant adeno-associated viral particles releasing SLMAP-shRNA precipitated reduced spontaneous contractile rate that was not fully recovered in SLMAP-depleted CMs challenged with isoproterenol (ISO), thus phenotypically mimicking heart failure performance. Interestingly, the overexpression of the SLMAP-3 full-length isoform induced a positive chronotropic effect in CMs that was more pronounced in response to ISO insult (vs. ISO-treated naïve CMs). Confocal live imaging showed that H9c2 cardiac myoblasts overexpressing SLMAP-3 exhibit a higher intracellular calcium transient peak when treated with ISO (vs. ISO-treated cells carrying a control adeno-associated viral particle). Proteomics revealed that SLMAP-3 interacts with the regulator of CM contraction, striatin. Collectively, our data demonstrate that SLMAP-3 is a novel regulator of CM contraction rate and their response to adrenergic stimuli. Loss of SLMAPs phenotypically mimics cardiac failure and crystallizes SLMAPs as predictive of dilated cardiomyopathy and heart failure.
Assuntos
Cálcio/metabolismo , Cardiomiopatia Dilatada/metabolismo , Regulação para Baixo , Ventrículos do Coração/metabolismo , Espaço Intracelular/metabolismo , Proteínas de Membrana/metabolismo , Miócitos Cardíacos/metabolismo , Animais , Cardiomiopatia Dilatada/tratamento farmacológico , Cardiomiopatia Dilatada/patologia , Cardiomiopatia Dilatada/fisiopatologia , Linhagem Celular , Regulação para Baixo/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Ventrículos do Coração/efeitos dos fármacos , Humanos , Espaço Intracelular/efeitos dos fármacos , Isoproterenol/farmacologia , Proteínas de Membrana/deficiência , Proteínas de Membrana/genética , Terapia de Alvo Molecular , Contração Miocárdica/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Isoformas de Proteínas/deficiência , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , RatosRESUMO
Circuit resistance training (CT) constitutes a high-intensity interval program commonly used to target weight loss; however, the loads and exercise patterns that maximize energy expenditure (EE) remain undetermined. We examined differences in EE among CT protocols using varying loads and contraction speeds in recreationally trained males and females. Seven males (age, 21.1 ± 0.5 years) and 8 females (age, 20.0 ± 0.9 years) performed 3 randomized CT protocols incorporating 3 circuits using heavy-load (80% 1-repetition maximum (1RM)) explosive (HLEC), heavy-load, controlled (2 s) (HLCC), and moderate-load (50% 1RM) explosive contractions (MLEC). Expired air was collected continuously before, during, and after exercise. Blood lactate was collected at rest, immediately postexercise, and 5 min postexercise. No significant differences were detected for resting EE; however, there was a significant difference among conditions during exercise (p = 0.034, ηp2 = 0.229). Post hoc analysis revealed that MLEC produced significantly higher EE than HLCC, but not HLEC (p = 0.023). There was a significant difference among conditions for rate of EE during exercise (p = 0.003, ηp2 = 0.361). Post hoc analysis revealed that HLEC produced a significantly higher EE rate than HLCC (p = 0.012) or MLEC (p = 0.001). A condition × sex interaction was seen for blood lactate changes (ηp2 = 0.249; p = 0.024). Females produced significantly greater change for MLEC than HLEC (p = 0.011), while males showed no significant differences. Our results favor CT using MLEC for a higher EE during a full workout; however, the rate of EE was highest when using HLEC.