AGT - Angiotensinogen | Elisa - Clia - Antibody - Protein

Background:

Angiotensinogen (AGT) is a protein primarily produced and secreted by the liver, although it is also synthesized by other tissues, including the kidney and adipose tissue. It serves as the precursor molecule for the renin-angiotensin system (RAS), a key regulatory pathway involved in blood pressure regulation, fluid balance, and electrolyte homeostasis. AGT is converted into angiotensin I by the enzyme renin, which is released by the kidneys in response to various stimuli, such as decreased blood pressure or sodium levels. Angiotensin I is further converted into angiotensin II by angiotensin-converting enzyme (ACE), leading to vasoconstriction, aldosterone release, and sodium reabsorption, ultimately raising blood pressure. Dysregulation of the RAS, including alterations in AGT levels, has been implicated in hypertension, cardiovascular disease, and kidney disorders. Therapeutic interventions targeting the RAS, such as ACE inhibitors and angiotensin receptor blockers, are commonly used to manage hypertension and related conditions. Understanding the role of AGT in the RAS provides insights into cardiovascular health and potential avenues for therapeutic intervention. Ongoing research continues to elucidate the intricate mechanisms underlying AGT regulation and its implications for human health and disease

Protein Structure:

• Molecular Weight: Approximately 52 kDa.
• Primary Structure: AGT is composed of 452 amino acids.
• Functional Domains: The protein includes a signal peptide for secretion, a reactive center loop for renin interaction, and a serpin-like structure. The critical renin cleavage site is between Leu10 and Val11 in the human sequence.
• Glycosylation: AGT is glycosylated at several sites, which is important for its stability and function.

Classification and Subtypes:

AGT belongs to the serpin (serine protease inhibitor) superfamily, although it does not inhibit proteases like most serpins. It is classified as a non-inhibitory serpin.

Function and Biological Significance:

• Renin-Angiotensin System: AGT is the precursor to angiotensin I. Renin cleaves AGT to produce angiotensin I, which is subsequently converted to angiotensin II by angiotensin-converting enzyme (ACE). Angiotensin II is a critical regulator of blood pressure, stimulating vasoconstriction, aldosterone release, and sodium retention.
• Blood Pressure Regulation: By influencing the production of angiotensin II, AGT indirectly controls vasoconstriction and fluid balance.
• Electrolyte Balance: Angiotensin II promotes sodium reabsorption and potassium excretion through aldosterone release from the adrenal cortex.

Interactions:

• Renin: The primary enzyme that interacts with AGT, cleaving it to produce angiotensin I.
• Angiotensin-Converting Enzyme (ACE): Converts angiotensin I to the active angiotensin II.
• Angiotensin Receptors (AT1 and AT2): Angiotensin II acts on these receptors to exert its physiological effects.
• Other Proteins: AGT can interact with various proteins involved in its processing, stability, and function, including enzymes and receptor proteins in the RAS.

Clinical Issues:

• Hypertension: Variations in AGT levels or mutations in the AGT gene can contribute to hypertension. Polymorphisms in the AGT gene are associated with an increased risk of developing high blood pressure.
• Cardiovascular Diseases: Elevated AGT levels are linked to cardiovascular diseases such as heart failure and coronary artery disease due to their role in the RAS.
• Kidney Diseases: The RAS is crucial in kidney function, and dysregulation of AGT can lead to conditions like chronic kidney disease and diabetic nephropathy.
• Genetic Polymorphisms: Certain polymorphisms, like the M235T variant, are associated with altered AGT levels and increased risk of hypertension and cardiovascular diseases.

Summary:

Angiotensinogen (AGT) is a vital precursor protein in the renin-angiotensin system, primarily produced by the liver. It plays an essential role in blood pressure regulation and fluid balance through its conversion to angiotensin I and subsequently angiotensin II, a potent vasoconstrictor. AGT's interactions with renin and ACE are crucial for its function. Clinical issues related to AGT include hypertension, cardiovascular diseases, and kidney disorders, often influenced by genetic polymorphisms in the AGT gene. Understanding AGT's structure, function, and interactions provides insights into its significant role in maintaining cardiovascular and renal health.