Abstract
ObjectiveResistance vessel remodeling is controlled by myriad of hemodynamic and neurohormonal factors. This study characterized structural and molecular remodeling in mesenteric resistance arteries (MRAs) in diabetic (db/db) and control (Db/db) mice.MethodsStructural properties were assessed in isolated MRAs from 12 and 16 wk-old db/db and Db/db mice by pressure myography. Matrix regulatory proteins were measured by Western blot analysis. Mean arterial pressure and superior mesenteric blood flow were measured in 12 wk-old mice by telemetry and a Doppler flow nanoprobe, respectively.ResultsBlood pressure was similar between groups. Lumen diameter and medial cross-sectional area were significantly increased in 16 wk-old db/db MRA compared to control, indicating outward hypertrophic remodeling. Moreover, wall stress and cross-sectional compliance were significantly larger in diabetic arteries. These remodeling indices were associated with increased expression of matrix regulatory proteins matrix metalloproteinase (MMP)-9, MMP-12, tissue inhibitors of matrix metalloproteinase (TIMP)-1, TIMP-2, and plasminogen activator inhibitor-1 (PAI-1) in db/db arteries. Finally, superior mesenteric artery blood flow was increased by 46% in 12 wk-old db/db mice, a finding that preceded mesenteric resistance artery remodeling.ConclusionsThese data suggest that flow-induced hemodynamic changes may supersede the local neurohormonal and metabolic milieu to culminate in hypertrophic outward remodeling of type 2 DM mesenteric resistance arteries.
Highlights
Diabetes mellitus (DM) is the fifth leading cause of death in the United States, and type 2 DM accounts for 90–95% of all diabetic cases for which vascular complications are a leading cause of morbidity, mortality and economic burden [1]
Mesenteric Resistance Artery Structure in 16 wk-old Mice mesenteric resistance arteries (MRAs) from 16 wk-old db/db mice had larger internal lumen diameter and external diameter measured at each pressure compared to MRAs isolated from control mice (Fig. 1a,b)
MRAs from db/db mice were more compliant at low pressures than control mice (Fig. 2a)
Summary
Diabetes mellitus (DM) is the fifth leading cause of death in the United States, and type 2 DM accounts for 90–95% of all diabetic cases for which vascular complications are a leading cause of morbidity, mortality and economic burden [1]. Vascular remodeling involves the reorganization of existing cells and extracellular matrix (ECM) or changes in vascular smooth muscle cell (VSMC) growth and migration [9], and can be characterized as hypertrophic (increased cross-sectional area), eutrophic (no change in cross-sectional area) or hypotrophic remodeling (reduced cross-sectional area). These processes have been associated with either inward remodeling (smaller lumen diameter) or outward remodeling (increased lumen diameter) [10]. Hypertensive patients with pre-existing type 2 DM had predominantly eutrophic remodeling and increased fibrosis [12]
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