Angiotensin-Converting Enzyme Production by Vascular Endothelial Cells
Angiotensin-converting enzyme (ACE) is predominantly produced by vascular endothelial cells. 1, 2, 3
Primary Site of ACE Production
Vascular endothelial cells are the main source of ACE in the human body, with the enzyme primarily localized on the luminal surface of these cells. This distribution is critical for the enzyme's physiological functions in the cardiovascular system:
- ACE is inserted at the cell membrane via its carboxyl terminus, functioning as an ectoprotein on the surface of endothelial cells 2
- Human plasma ACE originates from endothelial cells 2, 3
- ACE is concentrated predominantly in the fetal circulation, particularly in endothelial cells 1
Physiological Significance of Endothelial ACE
The strategic location of ACE on vascular endothelial cells allows it to perform crucial roles in cardiovascular homeostasis:
- Converts angiotensin I to the potent vasopressor angiotensin II
- Inactivates the vasodilator bradykinin
- Contributes to vascular tone regulation
- Participates in fluid-electrolyte balance
The incremental ACE protein expression in fetal endothelial cells throughout pregnancy favors enhanced angiotensin II production in placental vessels, which supports angiogenesis and fetal perfusion 1.
Other Cellular Sources of ACE
While vascular endothelial cells are the primary source, ACE is also produced by:
- Cells derived from the monocyte-macrophage system 3
- Various epithelial cells 2
- Germinal cells (producing a single-domain germinal form of ACE) 2
Regulation of Endothelial ACE Production
ACE activity in vascular endothelial cells is subject to regulation by various factors:
- Phorbol esters (like PMA) increase both cellular and medium ACE activity 4
- Cyclic AMP-related agents increase cellular but not medium ACE activity 4
- Lipopolysaccharides (LPS) can decrease endothelial ACE activity, which may contribute to hypotension in septic shock 5
Clinical Implications
The distribution and regulation of ACE have important clinical implications:
- ACE inhibitors target this enzyme to treat hypertension and protect against end-organ damage 2
- Decreased serum ACE activity has been reported in vascular pathologies involving endothelial abnormalities 3
- Increased serum ACE activity is seen in conditions involving stimulation of the monocytic cell line, particularly granulomatous diseases like sarcoidosis 3
Alternative Angiotensin II Forming Pathways
While ACE is the primary enzyme converting angiotensin I to angiotensin II, both vascular endothelial cells and vascular smooth muscle cells possess alternate angiotensin II forming pathways that are independent of ACE and renin 6. These alternative pathways may be clinically relevant when considering comprehensive RAAS blockade strategies.