Mechanical pressure unloading therapy reverses thoracic aortic structural and functional changes in a hypertensive rat model

Sevil Korkmaz-Icöz, Paige Brlecic, Mihály Ruppert, T. Radovits, Matthias Karck, G. Szabó

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)2350-2361
Number of pages12
JournalJournal of Hypertension
Volume36
Issue number12
DOIs
Publication statusPublished - Dec 1 2018

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Thorax
Tissue Inhibitor of Metalloproteinase-2
Endothelium
Blood Vessels
Pressure
Metalloproteases
Messenger RNA
Fibrosis
Collagen
Blood Pressure
Vasodilation
Therapeutics
Baths
Aorta
Body Weight
Hypertension
Gene Expression
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Mechanical pressure unloading therapy reverses thoracic aortic structural and functional changes in a hypertensive rat model. / Korkmaz-Icöz, Sevil; Brlecic, Paige; Ruppert, Mihály; Radovits, T.; Karck, Matthias; Szabó, G.

In: Journal of Hypertension, Vol. 36, No. 12, 01.12.2018, p. 2350-2361.

Research output: Contribution to journalArticle

Korkmaz-Icöz, Sevil ; Brlecic, Paige ; Ruppert, Mihály ; Radovits, T. ; Karck, Matthias ; Szabó, G. / Mechanical pressure unloading therapy reverses thoracic aortic structural and functional changes in a hypertensive rat model. In: Journal of Hypertension. 2018 ; Vol. 36, No. 12. pp. 2350-2361.
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AU - Karck, Matthias

AU - Szabó, G.

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AB - 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.

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