RESUMEN
The study of the population of muscle satellite cells (SC) is important to understand muscle regeneration and its involvement in the different dystrophic processes. We studied two dystrophic mouse models, Largemyd and Lama2dy2j/J, that show an intense and very similar pattern of muscle degeneration, but with differences in the expression of genes involved in the regeneration cascade. They are, therefore, interesting models to study possible differences in the mechanism of activation and action of satellite cells in the dystrophic muscle. The main objectives of this chapter are to describe the isolation and characterization of SC populations, evaluating the presence of myogenic and pluripotent stem cells markers in normal and dystrophic muscles.
Asunto(s)
Desarrollo de Músculos/fisiología , Músculo Esquelético/metabolismo , Distrofia Muscular Animal/patología , Regeneración/fisiología , Células Satélite del Músculo Esquelético/citología , Animales , Proliferación Celular/fisiología , Modelos Animales de Enfermedad , Citometría de Flujo , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Distrofias Musculares/patologíaRESUMEN
OBJECTIVE: The current study investigated the prevalence of white-coat hypertension (WCH) and white-coat uncontrolled hypertension (WUCH) throughout the age spectrum among individuals with office isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH) and systolic-diastolic hypertension (SDH) who were untreated or treated with antihypertensive medications, respectively. METHODS: We cross-sectionally evaluated 8809 untreated (42% males, 52.1â±â16.2 years) and 9136 treated (39% males, 59.7â±â14.5 years) individuals from two independent Brazilian populations who underwent home blood pressure monitoring. Participants were also categorized as younger (<40 years), intermediate (≥40 and <60 years) and older (≥60 years) age. RESULTS: Unadjusted and adjusted analyses showed that the frequency of WCH and WUCH was significantly greater (Pâ<â0.05) in ISH and IDH than SDH at all age groups. Logistic regression analysis adjusted for sex, BMI and studied population showed that, compared with SDH, ISH had in average 4.1, 3.1 and 1.6-fold greater risk of WCH and 3.3, 3.6 and 2.0-fold greater risk of WUCH at younger, intermediate and older ages, whereas IDH had in average 2.3, 2.6 and 2.0-fold greater risk of WCH and 3.8, 3.2 and 3.8-fold greater risk of WUCH at younger, intermediate and older ages, respectively. CONCLUSION: ISH and IDH were associated with higher prevalence of WCH and WUCH than SDH across all age spectrum. In addition, treated and untreated ISH individuals with age less than 60 years and treated IDH individuals of all ages had the highest risk of having WCH phenotypes.
Asunto(s)
Monitoreo Ambulatorio de la Presión Arterial , Hipertensión/epidemiología , Hipertensión de la Bata Blanca/epidemiología , Adulto , Anciano , Antihipertensivos/uso terapéutico , Presión Sanguínea , Brasil/epidemiología , Femenino , Humanos , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Prevalencia , Hipertensión de la Bata Blanca/tratamiento farmacológico , Hipertensión de la Bata Blanca/fisiopatologíaRESUMEN
Satellite cells (SCs) are the main muscle stem cells responsible for its regenerative capacity. In muscular dystrophies, however, a failure of the regenerative process results in muscle degeneration and weakness. To analyze the effect of different degrees of muscle degeneration in SCs behavior, we studied adult muscle of the dystrophic strains: DMDmdx, Largemyd, DMDmdx/Largemyd, with variable histopathological alterations. Similar results were observed in the dystrophic models, which maintained normal levels of PAX7 expression, retained the Pax7-positive SCs pool, and their proliferation capacity. Moreover, elevated expression of MYOG, an important myogenic factor, was also observed. The ability to form new fibers was verified by the presence of dMyHC positive regenerating fibers. However, those fibers had incomplete maturation characteristics, such as small and homogenous fiber caliber, which could contribute to their dysfunction. We concluded that dystrophic muscles, independently of their degeneration degree, retain their SCs pool with proliferating and regenerative capacities. Nonetheless, the maturation of these new fibers is incomplete and do not prevent muscle degeneration. Taken together, these results suggest that the improvement of late muscle regeneration should better contribute to therapeutic approaches.
Asunto(s)
Distrofias Musculares/patología , Distrofias Musculares/fisiopatología , Regeneración , Células Satélite del Músculo Esquelético/patología , Animales , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Antígeno Ki-67/metabolismo , Ratones Endogámicos C57BL , Ratones Endogámicos mdx , Desarrollo de Músculos/genética , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/patología , Factor de Transcripción PAX7/metabolismo , Células Satélite del Músculo Esquelético/metabolismoRESUMEN
The values used to define the presence of white-coat or masked blood pressure (BP) effects are arbitrary. The aim of this study was to investigate the accuracy of several cutoff points based on the difference between office and home BP (ΔBP) values to detect white-coat uncontrolled (WUCH) and masked uncontrolled (MUCH) hypertension, which are phenotypes with adverse prognoses, in a large cohort of treated hypertensive patients. This multicenter cross-sectional study included 6,049 treated hypertensive patients (40% males, mean age 59.1 ± 14.4 years) who underwent office and home BP monitoring. We compared the sensitivity, specificity, area under curve (AUC), and positive (PPV) and negative (NPV) predictive values of several ΔBP cutoffs to detect WUCH and MUCH. The 15/9 mmHg cutoff, which reflects a 1.0 standard deviation of the ΔBP, showed the best AUC (0.783, 95% CI = 0.772-0.794) for the detection of WUCH, particularly in individuals with office grade 1 hypertension (AUC = 0.811, 95% CI = 0.793-0.829). The -1/-1 mmHg cutoff, which considers all individuals who had lower systolic or diastolic BP levels in the office than at home, had the highest AUC (0.822, 95% CI = 0.808-0.836) for the detection of MUCH. Both cutoff values also had the best performances for identifying all patients with higher and lower office-than-home BP grades. In conclusion, the 15/9 and -1/-1 mmHg cutoffs showed the best performance for the detection of treated hypertensive patients with WUCH and MUCH, respectively, and therefore might be markers of significant white-coat and masked effects and could be useful for identifying preferential targets for more routine home BP measures.