A story of two ACEs

Area of Science:

• Cardiovascular Science
• Genetics
• Pharmacology

Background:

• Cardiovascular diseases are a leading cause of death globally.
• High blood pressure is a major risk factor for serious cardiovascular events.
• The renin-angiotensin system, targeted by ACE inhibitors, is crucial in managing hypertension and heart failure.

Purpose of the Study:

• To investigate the role of the newly characterized ACE2 gene in hypertension.
• To explore the relationship between ACE and ACE2 in cardiovascular regulation.

Main Methods:

• Mapping the ACE2 gene to quantitative trait loci in rat models of hypertension.
• Targeted disruption of the ACE2 gene in mice.
• Analyzing cardiac function and gene expression in ACE2-deficient mice.
• Comparing heart function in mice deficient in ACE2, ACE, or both.

Main Results:

• ACE2 gene maps to the X chromosome in hypertensive rat models, identifying it as a candidate gene for hypertension.
• ACE2 deficiency in mice led to elevated angiotensin II, impaired cardiac contractility, and cardiac gene upregulation.
• Mice lacking both ACE and ACE2 exhibited normal heart function, indicating a negative regulatory interaction between the two enzymes.

Conclusions:

• ACE2 plays a significant role in cardiovascular regulation and is implicated in hypertension.
• The interplay between ACE and ACE2 is complex and warrants further investigation.
• Understanding the ACE-ACE2 system offers new avenues for developing treatments for cardiovascular diseases.