The renin-angiotensin system in COVID-19: Why ACE2 targeting by coronaviruses produces higher mortality in elderly...

Area of Science:

• Cardiovascular Science
• Molecular Biology
• Genomics

Background:

• The renin-angiotensin system (RAS) plays a critical role in regulating blood pressure and fluid balance.
• Dysregulation of RAS is implicated in various cardiovascular diseases and stress responses.
• Recent evidence links altered RAS function to cardiorespiratory failure in coronavirus infections.

Purpose of the Study:

• To investigate the tissue-specific dependence on RAS mediators.
• To elucidate the topological hierarchy of RAS signaling.
• To understand the implications of RAS dysregulation in conditions like hypertension and COVID-19.

Main Methods:

• Expectation-maximization clustering of human tissue RNA expression data from BioGPS.
• Analysis of gene expression patterns for key RAS components like ACE, ACE2, AT1R, and MAS1.
• Correlation of RAS gene expression with tissue types and physiological functions.

Main Results:

• ACE and AT1R clustered with the prorenin receptor, indicating a specific pathway.
• ACE2 and MAS1 clustered with other RAS genes in tissues including liver, heart, skeletal muscle, kidney, and lungs.
• Increased renin secretion was linked to hypertension and vascular resistance, while reduced ACE2 activity contributed to vasoconstriction.

Conclusions:

• Tissue-specific expression patterns define RAS functional hierarchies.
• RAS dysregulation, particularly reduced ACE2 activity, contributes to vasoconstriction and poor tissue perfusion, relevant to COVID-19 comorbidities.
• Understanding RAS tissue dependence is crucial for developing targeted therapies for cardiovascular and infectious diseases.