Angiotensin Converting Enzyme (ACE) plays a central role in managing blood pressure and fluid balance. It is a major component of the Renin-Angiotensin-Aldosterone System (RAAS), which regulates vascular tone and salt retention. While high ACE levels are often associated with conditions like sarcoidosis, a low concentration in the bloodstream is also a significant finding. A low ACE reading indicates compromised underlying physiological processes, which can stem from chronic diseases, acute systemic injury, or genetic predisposition.
The Function and Production of Angiotensin Converting Enzyme
The primary function of ACE is to catalyze the conversion of inactive Angiotensin I into the vasoconstrictor Angiotensin II. Angiotensin II narrows blood vessels, increasing blood pressure and stimulating the release of aldosterone. Aldosterone promotes sodium and water retention by the kidneys, contributing to fluid homeostasis. ACE also contributes to blood vessel dilation by inactivating bradykinin, a peptide that promotes vessel widening.
ACE is a membrane-bound enzyme anchored to the surface of endothelial cells lining the vascular system. The highest concentration is found in the capillaries of the lungs, making this the main site where Angiotensin I is converted to Angiotensin II. Soluble ACE found in the serum is shed from these endothelial cell surfaces. The amount of circulating ACE therefore reflects the overall health and function of the body’s endothelial lining.
Chronic Conditions Associated with Reduced ACE Levels
Several long-term health issues can suppress the body’s ability to synthesize or maintain normal ACE concentrations. A well-established link exists with hypothyroidism, a condition marked by insufficient thyroid hormone production. Since thyroid hormones modulate the synthesis of many proteins, a deficit directly correlates with decreased ACE synthesis and lower circulating levels.
Chronic liver disease, particularly advanced stages like cirrhosis, can result in reduced systemic ACE. The liver synthesizes many circulating proteins and is involved in the metabolism of the RAAS cascade. Severe impairment of the liver’s synthetic capacity, a hallmark of end-stage failure, leads to a general reduction in the production of various circulating proteins, including ACE.
Chronic kidney disease (CKD) can also diminish systemic ACE levels, especially in advanced stages. Severe CKD is characterized by systemic inflammation and metabolic derangement. This dysfunction impacts the integrity of the vascular endothelium and impairs the synthesis or increases the degradation of circulating peptides, contributing to lower measured enzyme activity.
Medication Effects and Genetic Variations
The most common reason for a low ACE measurement in a clinical setting is the use of Angiotensin Converting Enzyme Inhibitors (ACEi). Medications like lisinopril or enalapril are prescribed to manage high blood pressure and heart failure. These drugs work by binding to the ACE enzyme, directly inhibiting its function and leading to circulating ACE values that are significantly lowered, often to undetectable levels.
A person’s natural, baseline ACE concentration is heavily influenced by genetics. A common variation, the Insertion/Deletion (I/D) polymorphism in the ACE gene, dictates an individual’s inherent enzyme level. People who inherit the insertion (I) allele have a naturally lower baseline ACE level compared to those who inherit the deletion (D) allele.
Individuals homozygous for the insertion allele (II genotype) have the lowest ACE levels, while those homozygous for the deletion allele (DD genotype) have the highest. This genetic factor accounts for a substantial portion of the variability in serum ACE activity observed across the general population. This low level is not a sign of disease but is a normal, non-pathological finding for that individual.
Acute Systemic Factors Leading to Low ACE
Certain acute, life-threatening conditions can cause a rapid and profound drop in ACE levels. Acute Respiratory Distress Syndrome (ARDS) involves massive inflammation and injury to the lung tissue. Since the lungs contain the greatest density of ACE-producing endothelial cells, the widespread destruction of these capillaries during ARDS eliminates the primary source of circulating ACE.
Severe systemic inflammation, such as sepsis or extensive trauma, can also reduce ACE concentration. The body’s response involves widespread endothelial damage throughout the vascular system, resulting in the loss of enzyme-producing cells. This acute destruction, coupled with the inflammatory cascade, impairs normal enzyme production and accelerates its clearance from the bloodstream.
Severe protein-energy malnutrition can impair the body’s ability to synthesize ACE. As a protein, ACE requires amino acid building blocks for its production. A severe deficiency in these essential nutrients, often coupled with electrolyte imbalances, disrupts the metabolic machinery, leading to a reduction in the synthesis of circulating proteins, including ACE.