RESUMO
The apolipoprotein E-deficient (apoE-/-) mouse model has advanced our understanding of cardiovascular disease mechanisms and experimental therapeutics. This spontaneous model recapitulates aspects of human atherosclerosis, and allows for the development of dissecting abdominal aortic aneurysms (AAAs) when combined with angiotensin II. We characterized apoE-/- rats and hypothesized that, similar to mice, they would develop dissecting AAAs. We created rats with a 16-bp deletion of the apoE gene using transcription activator-like effector nucleases. We imaged the suprarenal aorta for 28 days after implantation of miniosmotic pumps that infuse angiotensin II (AngII, 200 ng/kg/min). Blood pressure (BP), serum lipids and lipoproteins, and histology were also analyzed. These rats did not develop pathological aortic dissection, but we did observe a decrease in circumferential cyclic strain, a rise in BP, and microstructural changes in the aortic medial layer. We also measured increased serum lipids with and without administration of a high-fat diet, but did not detect atherosclerotic plaques. Chronic infusion of AngII did not lead to the formation of dissecting AAAs or atherosclerosis in the rats used in this study. While reduced amounts of atherosclerosis may explain this resistance to dissecting aneurysms, further investigation is needed to fully characterize species-specific differences.
Assuntos
Angiotensina II , Aorta Abdominal/metabolismo , Aneurisma da Aorta Abdominal/metabolismo , Dissecção Aórtica/metabolismo , Apolipoproteínas E/deficiência , Dissecção Aórtica/induzido quimicamente , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/genética , Animais , Aorta Abdominal/diagnóstico por imagem , Aorta Abdominal/patologia , Aorta Abdominal/fisiopatologia , Aneurisma da Aorta Abdominal/induzido quimicamente , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/genética , Apolipoproteínas E/genética , Aterosclerose/genética , Aterosclerose/metabolismo , Aterosclerose/patologia , Pressão Sanguínea , Colesterol/sangue , Modelos Animais de Doenças , Técnicas de Inativação de Genes , Predisposição Genética para Doença , Fenótipo , Ratos Sprague-Dawley , Ratos Transgênicos , Fatores de Tempo , Ultrassonografia DopplerRESUMO
Heat therapy has been shown to promote capillary growth in skeletal muscle and in the heart in several animal models, but the effects of this therapy on angiogenic signaling in humans are unknown. We evaluated the acute effect of lower body heating (LBH) and unilateral thigh heating (TH) on the expression of angiogenic regulators and heat shock proteins (HSPs) in healthy young individuals. Exposure to LBH (n = 18) increased core temperature (Tc) from 36.9 ± 0.1 to 37.4 ± 0.1°C (P < 0.01) and average leg skin temperature (Tleg) from 33.1 ± 0.1 to 39.6 ± 0.1°C (P < 0.01), but did not alter the levels of circulating angiogenic cytokines and bone marrow-derived proangiogenic cells (CD34(+)CD133(+)). In skeletal muscle, the change in mRNA expression from baseline of vascular endothelial growth factor (VEGF), angiopoietin 2 (ANGPT2), chemokines CCL2 and CX3CL1, platelet factor-4 (PF4), and several members of the HSP family was higher 30 min after the intervention in the individuals exposed to LBH (n = 11) compared with the control group (n = 12). LBH also reduced the expression of transcription factor FOXO1 (P = 0.03). Exposure to TH (n = 14) increased Tleg from 32.8 ± 0.2 to 40.3 ± 0.1°C (P < 0.05) but Tc remained unaltered (36.8 ± 0.1°C at baseline and 36.9 ± 0.1°C at 90 min). This intervention upregulated the expression of VEGF, ANGPT1, ANGPT2, CCL2, and HSPs in skeletal muscle but did not affect the levels of CX3CL1, FOXO-1, and PF4. These findings suggest that both LBH and TH increase the expression of factors associated with capillary growth in human skeletal muscle.
Assuntos
Moduladores da Angiogênese/metabolismo , Proteínas de Choque Térmico/biossíntese , Temperatura Alta , Hipertermia Induzida , Proteínas Musculares/metabolismo , Músculo Esquelético/fisiologia , Neovascularização Fisiológica/fisiologia , Feminino , Regulação da Expressão Gênica/fisiologia , Humanos , Masculino , Adulto JovemRESUMO
Maternal behaviors during pregnancy have been reported to impact offspring health in adulthood. In this article we explore the novel hypothesis that exercise during pregnancy can protect against chronic disease susceptibility in the offspring. To date, research has demonstrated that improvements in metabolic outcomes, cardiovascular risk, and cancer can occur in response to maternal exercise during pregnancy.
Assuntos
Doença Crônica/prevenção & controle , Suscetibilidade a Doenças , Exercício Físico , Gravidez , Doenças Cardiovasculares/prevenção & controle , Feminino , Humanos , Doenças Metabólicas/prevenção & controle , Neoplasias/prevenção & controle , Fatores de RiscoRESUMO
PURPOSE: Research has revealed the role of adverse behaviors during pregnancy on metabolic and cardiovascular health outcomes in offspring. However, minimal attention has been focused on positive prenatal behaviors, such as exercise, and the effect on offspring health outcomes. The objective of this investigation was to test the hypothesis that mothers who voluntarily exercise during pregnancy would improve endothelial function in offspring from exercising compared with sedentary mothers. METHODS: Female Sprague Dawley rats were divided into sedentary (n = 10) or exercise (n = 9) groups with, the exercise group having voluntary access to a running wheel throughout gestation. Litter characteristics (weight and size) were taken 1 d after birth. After weaning, offspring were placed in sedentary cages where they remained until 4 or 8 months of age. Offspring food consumption and cage activity were assessed during a 72-h interval at 2, 4, 6, and 8 months of age. The abdominal aortas of offspring were harvested at 4 or 8 months of age, and vascular function was assessed using cumulative doses of endothelium-dependent (acetylcholine/10(-10)-10(-4) M) and independent (sodium nitroprusside/10(-10)-10(-4) M) vasodilators. RESULTS: There were no significant differences in litter size and litter weight at weaning between the sedentary and exercise groups. Food consumption and wheel running activity did not differ between the sedentary and exercise offspring at 2, 4, 6, or 8 months of age. Vasorelaxation response to acetylcholine or sodium nitroprusside did not differ between the offspring from sedentary and exercise dams. CONCLUSIONS: Maternal voluntary wheel running during pregnancy does not significantly alter behavior or vascular function in adult offspring.