RESUMEN
Cardiovascular diseases (CVD) are the leading cause of death globally. In recent years, follistatin-like protein 1 (FSTL1) has been proposed as an emerging potential clinical biomarker of CVD, since its concentration is upregulated in heart failure. The aim of the present study was to evaluate the association of FSTL1 levels and classic biomarkers with the risk of CVD in Mexican population. A case-control study was carried out in patients with cardiovascular diseases (CVD), arterial hypertension, but not CVD (cardiovascular risk factor-CRF), and healthy controls (control group) from the Mexican Institute of Social Security. Lipid profile, homocysteine (Hcys), serum amyloid A (SAA), FSTL1 concentration, PON1 concentration and activities [Arylesterase (ARE), and Lactonase (LAC)] were evaluated. High levels of FSTL1 were found in the CRF group and a positive association of FSTL1 (OR = 4.55; 95% CI 1.29-16.04, p = 0.02) with the presence of arterial hypertension, as well as Hcys (OR, 3.09; 95% CI 1.23-7.76, p = 0.02) and SAA (OR, 1.03; 95% CI 1.01-1.05, p < 0.01) with the presence of CVD. LAC activity (OR, 0.26; 95% CI 0.07-0.94, p = 0.04) and PON1 concentration (OR, 0.17; 95% CI 0.05-0.62, p = 0.01) were associated with a decrease in OR belonging to the group with CVD. Our results suggest that FSTL1 may be a useful biomarker for monitoring cardiovascular risk in clinical settings. However, longitudinal studies are needed to evaluate how FSTL1 could influence the association of PON1 activity and Hcys with CVD.
Asunto(s)
Biomarcadores , Enfermedades Cardiovasculares , Proteínas Relacionadas con la Folistatina , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Arildialquilfosfatasa/sangre , Biomarcadores/sangre , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/sangre , Estudios de Casos y Controles , Proteínas Relacionadas con la Folistatina/sangre , Hipertensión/epidemiología , Hipertensión/sangre , Hipertensión/diagnóstico , México/epidemiología , Medición de Riesgo/métodos , Factores de RiesgoRESUMEN
Inflammatory processes play a pivotal role in the development and progression of depression. Since Follistatin-like protein 1 (FSTL1) has been identified as a novel inflammatory protein, a variety of studies suggest that targeting FSTL1 may be useful in the treatment of diseases in which inflammation plays a central role. In the study, we aimed to investigate the causal relationship between FSTL1 signaling and the development of depression. To explore the effect and mechanism of FSTL1 on chronic stress-induced depression, the chronic unpredictable mild stress (CUMS) paradigm was used. Animals subjected to CUMS for 4 weeks exhibited depressive-like symptoms, including decreased sucrose preference and obvious behavioral despair, concomitantly with increased FSTL1 level in the hippocampus. In contrast, mice with FSTL1 knockdown abolished CUMS induced depression-like and anxiety-like behaviors. Moreover, FSTL1 knockdown reversed CUMS induced synaptic plasticity deficits in the PP-DG pathway of the hippocampus and increased the expression of synaptic associated proteins in the hippocampus of CUMS exposed mice. Microglia activation induced by CUMS paradigm could be significantly inhibited by FSTL1 knockdown. Furthermore, Western blot revealed that FSTL1 knockdown considerably decreased the expression of indicated molecules TLR4/MyD88/NF-κB signaling pathway in CUMS exposed mice. In conclusion, our data implies that FSTL1 may modulate the microglial activation through TLR4/MyD88/NF-κB signaling, which affects depression-like behaviors and synaptic function deficits induced by CUMS in mice. These results suggested that the role of FSTL1 in mediating microglia-related mechanisms in depression may shed light on developing new therapeutic strategies to treat this prevalent disease.