SMC Abca1 and Abcg1 Deficiency Enhances Urinary Bladder Distension but Not Atherosclerosis

Area of Science:

• Cardiovascular Biology
• Vascular Smooth Muscle Cell Biology
• Atherosclerosis Research

Background:

• Smooth muscle cells (SMCs) control blood flow via α-adrenergic receptors (α-ARs).
• Plasma membrane cholesterol accumulation impairs α1-AR signaling and SMC contractile function.
• ABCA1 and ABCG1 mediate cholesterol efflux to HDL, with differential expression in atherosclerotic plaques.

Purpose of the Study:

• To investigate the role of SMC-specific Abca1 and Abcg1 in regulating vasoconstriction and atherogenesis.
• To determine the impact of SMC cholesterol accumulation on SMC function and vascular disease.

Main Methods:

• Generated SMC-specific Abca1/Abcg1 deficient mice on an Ldlr knockout background.
• Fed mice a Western-type diet to induce hyperlipidemia and atherogenesis.
• Assessed vasoconstriction, urinary bladder function, SMC markers, and atherosclerotic lesion development.

Main Results:

• SMC-specific Abca1/Abcg1 deficiency enhanced α1-AR-mediated vasoconstriction and caused significant urinary bladder distension.
• Bladder SMCs from deficient mice showed transdifferentiation, cholesterol accumulation, and endoplasmic reticulum stress.
• Thoracic aorta SMCs did not exhibit transdifferentiation, and atherosclerotic lesion size was unaffected.

Conclusions:

• SMC cholesterol efflux pathways are critical for suppressing α1-AR-mediated vasoconstriction and preventing bladder SMC transdifferentiation and distension.
• This finding offers a potential mechanistic link between urinary bladder distension, diabetes, and impaired cholesterol efflux.
• Abca1/Abcg1 deficiency in intimal SMCs did not impact atherosclerotic plaque development.