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Mechanical pressure unloading therapy reverses thoracic aortic structural and functional changes in a hypertensive rat model.
J Hypertens 2018; 36(12):2350-2361JH

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.

Authors+Show Affiliations

Department of Cardiac Surgery, Heidelberg University Hospital, Heidelberg, Germany.Department of Cardiac Surgery, Heidelberg University Hospital, Heidelberg, Germany.Department of Cardiac Surgery, Heidelberg University Hospital, Heidelberg, Germany. Heart and Vascular Center, Department of Cardiology, Semmelweis University, Budapest, Hungary.Heart and Vascular Center, Department of Cardiology, Semmelweis University, Budapest, Hungary.Department of Cardiac Surgery, Heidelberg University Hospital, Heidelberg, Germany.Department of Cardiac Surgery, Heidelberg University Hospital, Heidelberg, Germany.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30045361

Citation

Korkmaz-Icöz, Sevil, et al. "Mechanical Pressure Unloading Therapy Reverses Thoracic Aortic Structural and Functional Changes in a Hypertensive Rat Model." Journal of Hypertension, vol. 36, no. 12, 2018, pp. 2350-2361.
Korkmaz-Icöz S, Brlecic P, Ruppert M, et al. Mechanical pressure unloading therapy reverses thoracic aortic structural and functional changes in a hypertensive rat model. J Hypertens. 2018;36(12):2350-2361.
Korkmaz-Icöz, S., Brlecic, P., Ruppert, M., Radovits, T., Karck, M., & Szabó, G. (2018). Mechanical pressure unloading therapy reverses thoracic aortic structural and functional changes in a hypertensive rat model. Journal of Hypertension, 36(12), pp. 2350-2361. doi:10.1097/HJH.0000000000001853.
Korkmaz-Icöz S, et al. Mechanical Pressure Unloading Therapy Reverses Thoracic Aortic Structural and Functional Changes in a Hypertensive Rat Model. J Hypertens. 2018;36(12):2350-2361. PubMed PMID: 30045361.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mechanical pressure unloading therapy reverses thoracic aortic structural and functional changes in a hypertensive rat model. AU - Korkmaz-Icöz,Sevil, AU - Brlecic,Paige, AU - Ruppert,Mihály, AU - Radovits,Tamás, AU - Karck,Matthias, AU - Szabó,Gábor, PY - 2018/7/26/pubmed PY - 2019/9/17/medline PY - 2018/7/26/entrez SP - 2350 EP - 2361 JF - Journal of hypertension JO - J. Hypertens. VL - 36 IS - 12 N2 - 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. SN - 1473-5598 UR - https://www.unboundmedicine.com/medline/citation/30045361/Mechanical_pressure_unloading_therapy_reverses_thoracic_aortic_structural_and_functional_changes_in_a_hypertensive_rat_model L2 - http://Insights.ovid.com/pubmed?pmid=30045361 DB - PRIME DP - Unbound Medicine ER -