Changes in vascular reactivity and endothelial Ca²⁺ dynamics with chronic low flow

Area of Science:

• Cardiovascular Biology
• Endothelial Cell Physiology
• Vascular Remodeling

Background:

• Blood flow disruption is linked to endothelial dysfunction, vascular remodeling, and atherosclerosis.
• Local calcium (Ca2+) signals in the endothelium are crucial for vascular function.
• Understanding how altered blood flow impacts endothelial Ca2+ signaling is vital for vascular disease research.

Purpose of the Study:

• To investigate the effects of chronic low blood flow on endothelial Ca2+ signal patterning.
• To correlate changes in Ca2+ dynamics with vascular structure and function alterations.
• To determine if impaired Ca2+ signaling contributes to endothelial dysfunction in a mouse model.

Main Methods:

• Surgical ligation (PL) of mouse carotid arteries to induce chronic low flow for two weeks.
• Histological analysis to assess vascular remodeling (e.g., neointima formation).
• Isometric force measurements to evaluate vascular contractility.
• Confocal imaging and custom analysis to assess endothelial Ca2+ dynamics.
• Measurement of endothelium-dependent vasorelaxation in response to acetylcholine (ACh).

Main Results:

• PL arteries exhibited significant remodeling compared to control arteries, including neointima formation.
• Vascular smooth muscle function was altered, with increased phenylephrine (PE)-induced contractions and decreased KCl-induced contractions.
• Endothelium-dependent vasorelaxation to ACh was significantly impaired in PL arteries.
• Endothelial Ca2+ imaging revealed impaired dynamics, characterized by fewer active sites and truncated Ca2+ events in PL arteries.

Conclusions:

• Chronic low blood flow induces significant vascular remodeling and endothelial dysfunction.
• Impairment of endothelial Ca2+ signal spatial and temporal patterns is a key feature of flow-disrupted vessels.
• Altered endothelial Ca2+ dynamics are associated with attenuated vasorelaxation and may underlie vascular disease progression.