Small artery remodeling depends on tissue-type transglutaminase

Area of Science:

• Vascular Biology
• Biochemistry
• Cardiovascular Physiology

Background:

• Small artery remodeling is crucial for regulating blood pressure and organ perfusion.
• Non-growth-related reorganization of vessel wall components significantly impacts vessel diameter.

Purpose of the Study:

• To investigate the role of tissue-type transglutaminase (tTG) in the inward remodeling of small arteries.
• To explore tTG as a potential therapeutic target for pathologies involving resistance artery remodeling.

Main Methods:

• In vivo studies using rat mesenteric arteries subjected to low blood flow.
• In vitro experiments with rat skeletal muscle and porcine coronary arteries.
• Western blot, immunostaining, and collagen gel contraction assays.
• Pharmacological inhibition of tTG and use of nitric oxide donors.

Main Results:

• Inhibition of tTG attenuated inward remodeling of rat mesenteric arteries induced by low blood flow.
• tTG inhibitors blocked endothelin-1-induced inward remodeling in rat arteries.
• Exogenous transglutaminase induced inward remodeling in rat and pig arteries, reversible by nitric oxide.
• Enhanced tTG expression increased inward remodeling in porcine coronary arteries.
• tTG activity was pressure-dependent, and its inhibition reversed remodeling, increasing vessel diameter.
• tTG mediated collagen compaction by smooth muscle cells in a gel assay.

Conclusions:

• Small artery remodeling associated with chronic vasoconstriction is dependent on tissue-type transglutaminase.
• tTG plays a significant role in the structural changes of resistance arteries.
• Targeting tTG may offer a novel therapeutic strategy for diseases characterized by inward arterial remodeling.