Journal of hypertension · 2018
Mechanical pressure unloading therapy reverses thoracic aortic structural and functional changes in a hypertensive rat model.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
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Korkmaz-Icöz Sevil, Brlecic Paige, Ruppert Mihály, Radovits Tamás, Karck Matthias, Szabó Gábor
Аннотация
OBJECTIVES: Hypertension can impair structure and function of blood vessels. Experimental data describing the reverse remodeling process after a mechanical pressure unloading therapy in the vasculature is limited. We studied the influence of pressure unloading on both the structural and functional alterations of the aorta in a hypertensive rat model.
METHODS: Using isolated thoracic aortic rings in an in-vitro organ bath system, endothelium-dependent and endothelium-independent vasorelaxation were studied 6-weeks or 12-weeks after abdominal aortic banding (aortic banding-6-week or aortic banding-12-week), and 6-weeks after an aortic debanding procedure performed after the sixth experimental week of aortic banding (aortic banding + debanding-12-week). Age-matched rats were sham-operated (sham-6-week or sham-12-week). The aortic morphometry and histological fibrosis were studied, and the mRNA-expression of metalloproteinase (MMP)-2, tissue inhibitor of metalloproteinase (TIMP)-2, and soluble guanylate cyclase subunits GUCY1a3 and GUCY1b3 were determined.
RESULTS: Aortic banding significantly increased systolic, diastolic, and pulse pressures. Structural changes (increased intima-media thickness and area normalized to body weight, aortic collagen content, higher MMP-2 and TIMP-2, and lower GUCY1a3 and GUCY1b3 mRNA-levels) and functional alterations (impaired endothelium-dependent and endothelium-independent vasorelaxation) have already taken place after 6 weeks of aortic banding. Pressure unloading, after established vascular changes, improved vascular function, resulted in reduced collagen content, and decreased both MMP-2 and TIMP-2 mRNA-expression.
CONCLUSION: Pressure-overload-induced vascular changes regressed due to mechanical unloading. Furthermore, debanding leads to a reductive tendency in fibrosis-associated gene expression and collagen accumulation. Collectively, the addition of drugs that target fibrosis to existing hypertensive treatment may present an attractive therapy against vascular remodeling.
METHODS: Using isolated thoracic aortic rings in an in-vitro organ bath system, endothelium-dependent and endothelium-independent vasorelaxation were studied 6-weeks or 12-weeks after abdominal aortic banding (aortic banding-6-week or aortic banding-12-week), and 6-weeks after an aortic debanding procedure performed after the sixth experimental week of aortic banding (aortic banding + debanding-12-week). Age-matched rats were sham-operated (sham-6-week or sham-12-week). The aortic morphometry and histological fibrosis were studied, and the mRNA-expression of metalloproteinase (MMP)-2, tissue inhibitor of metalloproteinase (TIMP)-2, and soluble guanylate cyclase subunits GUCY1a3 and GUCY1b3 were determined.
RESULTS: Aortic banding significantly increased systolic, diastolic, and pulse pressures. Structural changes (increased intima-media thickness and area normalized to body weight, aortic collagen content, higher MMP-2 and TIMP-2, and lower GUCY1a3 and GUCY1b3 mRNA-levels) and functional alterations (impaired endothelium-dependent and endothelium-independent vasorelaxation) have already taken place after 6 weeks of aortic banding. Pressure unloading, after established vascular changes, improved vascular function, resulted in reduced collagen content, and decreased both MMP-2 and TIMP-2 mRNA-expression.
CONCLUSION: Pressure-overload-induced vascular changes regressed due to mechanical unloading. Furthermore, debanding leads to a reductive tendency in fibrosis-associated gene expression and collagen accumulation. Collectively, the addition of drugs that target fibrosis to existing hypertensive treatment may present an attractive therapy against vascular remodeling.