RESUMEN
Patients with peripheral artery disease (PAD) have reduced muscle capillary density. Walking training (WT) is recommended for PAD patients. The goal of the study was to verify whether WT promotes angiogenesis in PAD-affected muscle and to investigate the possible role of miRNA-126 and the vascular endothelium growth factor (VEGF) angiogenic pathways on this adaptation. Thirty-two men with PAD were randomly allocated to two groups: WT (n = 16, 2 sessions/week) and control (CO, n = 16). Maximal treadmill tests and gastrocnemius biopsies were performed at baseline and after 12 weeks. Histological and molecular analyses were performed by blinded researchers. Maximal walking capacity increased by 65% with WT. WT increased the gastrocnemius capillary-fiber ratio (WT = 109 ± 13 vs. 164 ± 21 and CO = 100 ± 8 vs. 106 ± 6%, p < 0.001). Muscular expression of miRNA-126 and VEGF increased with WT (WT = 101 ± 13 vs. 130 ± 5 and CO = 100 ± 14 vs. 77 ± 20%, p < 0.001; WT = 103 ± 28 vs. 153 ± 59 and CO = 100 ± 36 vs. 84 ± 41%, p = 0.001, respectively), while expression of PI3KR2 decreased (WT = 97 ± 23 vs. 75 ± 21 and CO = 100 ± 29 vs. 105 ± 39%, p = 0.021). WT promoted angiogenesis in the muscle affected by PAD, and miRNA-126 may have a role in this adaptation by inhibiting PI3KR2, enabling the progression of the VEGF signaling pathway.
Asunto(s)
MicroARNs , Enfermedad Arterial Periférica , Masculino , Humanos , Claudicación Intermitente/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Enfermedad Arterial Periférica/genética , Enfermedad Arterial Periférica/metabolismo , Músculo Esquelético/metabolismo , Caminata/fisiología , MicroARNs/genética , MicroARNs/metabolismoRESUMEN
OBJECTIVE: To evaluate the effects of a progressive resistance training (RT) on cardiac autonomic modulation and on cardiovascular responses to autonomic stress tests in patients with Parkinson disease (PD). DESIGN: Randomized clinical trial. SETTING: The Brazil Parkinson Association. PARTICIPANTS: Patients (N=30) with PD (modified Hoehn & Yahr stages 2-3) were randomly divided into 2 groups: a progressive RT group (PD training [PDT] group) and a control group (PD control [PDC] group). In addition, a group of paired healthy control (HC) subjects without PD was evaluated. INTERVENTIONS: The PDT group performed 5 resistance exercises, 2 to 4 sets, 12 to 6 repetitions maximum per set. Individuals in the PDC group maintained their usual lifestyle. MAIN OUTCOME MEASURES: The PDT and PDC groups were evaluated before and after 12 weeks. The HC group was evaluated once. Autonomic function was assessed by spectral analysis of heart rate variability and cardiovascular responses to autonomic stress tests (deep breathing, Valsalva maneuver, orthostatic stress). RESULTS: Compared with baseline, the normalized low-frequency component of heart rate variability decreased significantly after 12 weeks in the PDT group only (PDT: 61±17 normalized units [nu] vs 47±20nu; PDC: 60±14nu vs 63±10nu; interaction P<.05). A similar result was observed for systolic blood pressure fall during orthostatic stress that also was reduced only in the PDT group (PDT: -14±11mmHg vs -6±10mmHg; PDC: -12±10mmHg vs -11±10mmHg; interaction P<.05). In addition, after 12 weeks, these parameters in the PDT group achieved values similar to those in the HC group. CONCLUSIONS: In patients with PD, progressive RT improved cardiovascular autonomic dysfunction.
Asunto(s)
Sistema Nervioso Autónomo/fisiopatología , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/rehabilitación , Entrenamiento de Fuerza/métodos , Factores de Edad , Anciano , Presión Sanguínea , Brasil , Femenino , Frecuencia Cardíaca , Humanos , Masculino , Persona de Mediana Edad , Fuerza Muscular/fisiología , Estudios Prospectivos , SexoRESUMEN
OBJECTIVE: To investigate submaximal and maximal responses during maximal cardiopulmonary exercise tests in subjects with Parkinson disease (PD). DESIGN: Cross-sectional. SETTING: A PD association. PARTICIPANTS: A sample (N=68) of subjects with PD (n=48; mean age, 66±8y; modified Hoehn and Yahr stage between 2 and 3; "on" state of medication) and age-matched controls without PD (n=20; mean age, 64±9y). INTERVENTIONS: Maximal cardiopulmonary exercise test on a cycle ergometer. MAIN OUTCOME MEASURES: Oxygen uptake (VËo2), systolic blood pressure (SBP), and heart rate assessed at rest, submaximal intensities (ie, anaerobic threshold [AT] and respiratory compensation point), and maximal intensity (peak exercise). RESULTS: Compared with control subjects, subjects with PD had lower VËo2, heart rate, and SBP at respiratory compensation point and peak exercise (VËo2: 14.6±3.6mLâ kgâ min vs 17.9±5.5mLâ kgâ min and 17.7±4.8mLâ kgâ min vs 21.5±6.6mLâ kgâ min; heart rate: 119±17beats/min vs 139±12beats/min and 132±20beats/min vs 158±13beats/min; SBP: 151±17mmHg vs 172±20mmHg and 166±21mmHg vs 187±24mmHg; P≤.05). They also had lower heart rate at AT (102±14beats/min vs 110±13beats/min; P≤.05), whereas VËo2 and SBP at this intensity were similar to those of control subjects. CONCLUSIONS: Subjects with PD demonstrated blunted metabolic and cardiovascular responses to submaximal and maximal exercise tests, especially at intensities above AT, which are in line with autonomic disturbances present in patients with PD. Future studies need to determine how this affects performance, participation, and responses of these patients to exercise training at different intensities.
Asunto(s)
Prueba de Esfuerzo/estadística & datos numéricos , Ejercicio Físico/fisiología , Enfermedad de Parkinson/fisiopatología , Anciano , Umbral Anaerobio , Presión Sanguínea , Estudios de Casos y Controles , Estudios Transversales , Tolerancia al Ejercicio , Femenino , Frecuencia Cardíaca , Humanos , Masculino , Persona de Mediana Edad , Consumo de OxígenoRESUMEN
PURPOSE: MicroRNA (miRNA)-126 is angiogenic and has two validated targets: Sprouty-related protein 1 (Spred-1) and phosphoinositol-3 kinase regulatory subunit 2 (PI3KR2), negative regulators of angiogenesis by VEGF pathway inhibition. We investigated the role of swimming training on cardiac miRNA-126 expression related to angiogenesis. METHODS: Female Wistar rats were assigned to three groups: sedentary (S), training 1 (T1, moderate volume), and training 2 (T2, high volume). T1 consisted of 60 min·d of swimming, five times per week for 10 wk with 5% body overload. T2 consisted of the same protocol of T1 until the eighth week; in the ninth week, rats trained for two times a day, and in the 10th week, rats trained for three times a day. MiRNA and PI3KR2 gene expression analysis was performed by real-time polymerase chain reaction in heart muscle. We assessed markers of training, the cardiac capillary-fiber ratio, cardiac protein expression of VEGF, Spred-1, Raf-1/ERK 1/2, and PI3K/Akt/eNOS. RESULTS: The cardiac capillary-fiber ratio increased in T1 (58%) and T2 (101%) compared with S. VEGF protein expression was increased 42% in T1 and 108% in T2. Cardiac miRNA-126 expression increased 26% (T1) and 42% (T2) compared with S, correlated with angiogenesis. The miRNA-126 target Spred-1 protein level decreased 41% (T1) and 39% (T2), which consequently favored an increase in angiogenic signaling pathway Raf-1/ERK 1/2. On the other hand, the gene expression of PI3KR2, the other miRNA-126 target, was reduced 39% (T1) and 78% (T2), and there was an increase in protein expression of components of the PI3K/Akt/eNOS signaling pathway in the trained groups. CONCLUSIONS: This study showed that aerobic training promotes an increase in the expression of miRNA-126 and that this may be related to exercise-induced cardiac angiogenesis, by indirect regulation of the VEGF pathway and direct regulation of its targets that converged in an increase in angiogenic pathways, such as MAPK and PI3K/Akt/eNOS.