Angiotensin-converting enzyme, known as ACE, is produced primarily by the cells lining your blood vessels, with the lungs serving as the single largest source. The enzyme plays a central role in regulating blood pressure, and understanding where it originates helps explain why ACE inhibitors (a common class of blood pressure medication) work the way they do.
The Lungs Are the Main Production Site
ACE is made by endothelial cells, the thin layer of cells that coat the inside of every blood vessel in your body. While these cells produce ACE throughout your circulatory system, the capillary blood vessels in the lungs are the dominant site of both ACE production and its activity. The lung’s vast capillary network gives it an enormous surface area of endothelial cells, making it a factory for generating the enzyme that enters your bloodstream.
This is why the lungs function almost like a hormone-producing organ. Blood passes through the lung capillaries, where ACE converts a relatively inactive protein fragment called angiotensin I into angiotensin II, a potent molecule that constricts blood vessels and raises blood pressure. Your kidneys also contribute ACE, but the lungs are responsible for the bulk of what circulates in your blood.
Other Tissues That Produce ACE
Beyond the vascular lining, ACE appears on the surface of several other cell types. Epithelial cells (the cells that line organs and glands), certain brain cells, and immune cells like macrophages and dendritic cells all produce the enzyme. This wider distribution suggests ACE does more than just regulate blood pressure; it participates in immune responses and tissue remodeling as well.
There is also a distinct form of ACE found in the male reproductive system. Glandular cells in the epididymis and prostate produce ACE that ends up in seminal fluid. This version of the enzyme has a slightly different shape than the lung-derived form, and it’s encoded by the same gene but processed differently. The gene responsible, located on chromosome 17, uses alternative splicing to produce both the standard “somatic” version found throughout the body and a testis-specific version involved in male fertility.
How ACE Fits Into Blood Pressure Regulation
ACE is one link in a chain reaction called the renin-angiotensin-aldosterone system, or RAAS. When your blood pressure drops or your kidneys detect low blood flow, your kidneys release an enzyme called renin. Renin clips a protein made by your liver into angiotensin I, which is essentially a precursor with little biological punch on its own. ACE in your lungs and kidneys then splits angiotensin I into angiotensin II, the molecule that actually raises blood pressure by tightening blood vessels and triggering your adrenal glands to retain salt and water.
This is exactly the step that ACE inhibitor medications block. By reducing the enzyme’s ability to produce angiotensin II, these drugs keep blood vessels relaxed and blood pressure lower.
ACE vs. ACE2
ACE2 gained widespread attention during the COVID-19 pandemic because the virus uses it as an entry point into cells. Despite the similar name, ACE2 works in the opposite direction from ACE. While ACE generates angiotensin II (which raises blood pressure), ACE2 breaks angiotensin II down into smaller fragments that relax blood vessels and reduce inflammation. The two enzymes share about 40% of their structure, but ACE2 is not affected by standard ACE inhibitor medications.
Together, ACE and ACE2 act as a balancing system. ACE ramps up blood pressure signals, and ACE2 dials them back. When this balance is disrupted, cardiovascular and lung problems can follow.
An Ancient Enzyme
ACE is not unique to humans. Versions of the enzyme exist across an extraordinary range of species, including insects and even bacteria. A plant-infecting bacterium called Xanthomonas carries an ACE protein capable of converting angiotensin I to angiotensin II, suggesting the enzyme’s core function is hundreds of millions of years old. In fruit flies, an ACE-like enzyme plays a role in processing proteins in seminal fluid, paralleling the reproductive function seen in humans. The evolutionary persistence of ACE across such different organisms points to how fundamental its protein-cutting ability is to basic biological processes.
The Discovery of ACE
The enzyme was first identified in 1956 by researcher Leonard Skeggs and colleagues, who demonstrated that angiotensin II is created when ACE cleaves angiotensin I. That finding, published in the Journal of Experimental Medicine, launched decades of drug development that eventually produced ACE inhibitors, one of the most widely prescribed classes of medications in the world. The basic outline of the blood pressure regulation system was already known in the 1950s, but pinpointing ACE as the critical conversion step gave scientists a specific target to design drugs around.