Pathophysiologic implications of angiotensin I-converting enzyme as a mechanosensor: diabetes

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Pathophysiology

Background:

• Somatic angiotensin I-converting enzyme (ACE) is proposed as a mechanosensor.
• This hypothesis suggests tissue ACE activation by turbulent blood flow initiates age-dependent diseases.
• ACE activation may be the first step in disease-related "cascades".

Purpose of the Study:

• To explore the "ACE as mechanosensor" hypothesis.
• To investigate its utility in explaining the molecular pathogenesis of diabetes and its complications.
• To assess the potential of ACE inhibition in delaying aging-related diseases.

Main Methods:

• Review and theoretical exploration of the "ACE as mechanosensor" hypothesis.
• Analysis of ACE's role in the molecular pathogenesis of diabetes and accelerated aging.

Main Results:

• The hypothesis provides a potential molecular origin for numerous adult diseases, including diabetes, cancer, autoimmune, and psychiatric disorders.
• It links the vasculature and turbulent blood flow to the initiation of age-dependent diseases.
• Tissue ACE activation is posited as an early event in disease cascades.

Conclusions:

• The "ACE as mechanosensor" hypothesis offers a novel framework for understanding the origin of many age-dependent diseases.
• It highlights the potential significance of vascular mechanics in disease initiation.
• Inhibiting tissue ACE may represent a therapeutic strategy to delay the progression of common aging-related diseases, particularly diabetes.