What cell type is primarily responsible for producing Angiotensin-Converting Enzyme (ACE)?

Angiotensin-Converting Enzyme Production in the Body

Vascular endothelial cells are the primary cell type responsible for producing Angiotensin-Converting Enzyme (ACE). 1

Main Sources of ACE Production

• ACE is predominantly expressed in vascular endothelial cells throughout the body, where it functions as an ecto-enzyme facing the vascular lumen 2
• ACE is concentrated in the fetal circulation, particularly in endothelial cells, with incremental protein expression throughout pregnancy 1
• ACE is also found in the endothelium of both the intima and the vasa vasorum of the adventitia in large blood vessels 3
• Cells derived from the monocyte-macrophage system can also produce ACE, particularly in granulomatous diseases 4

Physiological Role of ACE

• ACE is a zinc-metallopeptidase that converts angiotensin I to the potent vasoconstrictor angiotensin II and degrades bradykinin, a powerful vasodilator 2
• ACE is a key enzyme in the renin-angiotensin-aldosterone system (RAAS), which regulates blood pressure, fluid-electrolyte balance, and cardiovascular function 1, 5
• In pregnancy, ACE plays a crucial role in placentation, trophoblast invasion, and spiral artery remodeling 1
• The incremental ACE expression in fetal endothelial cells throughout pregnancy enhances angiotensin II production in placental vessels, supporting angiogenesis and fetal perfusion 1

Molecular Structure and Forms of ACE

• ACE exists in two forms in humans: the ubiquitous somatic ACE with two tandem active sites and the sperm-specific germinal ACE with a single active site 6
• ACE is a monomeric, membrane-bound enzyme that requires zinc and chloride for its catalytic activity 6
• The enzyme can be released from the cell membrane by specific metalloproteases, resulting in soluble forms of both isoenzymes in plasma 2

Regulation of ACE Production

• Phorbol 12-myristate 13-acetate (PMA) increases both cellular and medium ACE activity in endothelial cells 7
• cAMP-related agents can increase cellular ACE activity without affecting medium ACE activity 7
• Estrogens can regulate ACE expression and activity, particularly during pregnancy 1

Clinical Significance

• Increased serum ACE activity is observed in granulomatous diseases like sarcoidosis, silicosis, and asbestosis 4
• Decreased serum ACE activity is seen in vascular pathologies involving endothelial abnormalities, such as deep vein thrombosis 2
• ACE inhibitors are cornerstone treatments for cardiovascular diseases including hypertension, heart failure, and post-myocardial infarction care 5
• ACE2, a homolog of ACE, has been identified as the receptor for SARS-CoV-2, the virus causing COVID-19 1