ANGPTL - Angiopoietin Like | Elisa - Clia - Antibody - Protein

Background:

ANGPTL or Angiopoietin-Like proteins are a family of proteins structurally similar to the angiopoietins but do not bind to the Tie-2 receptor like the classical angiopoietins. Instead, ANGPTLs have diverse functions and are involved in various biological processes, including lipid metabolism, glucose homeostasis, and regulation of angiogenesis.ANGPTL1 is involved in the regulation of angiogenesis and has been found to inhibit endothelial cell migration, which is important for controlling blood vessel formation. ANGPTL2: This protein is involved in inflammation, angiogenesis, and extracellular matrix remodeling. ANGPTL2 has been linked to various diseases, including cardiovascular disease, diabetes, and cancer. ANGPTL3 plays a role in lipid metabolism. It inhibits lipoprotein lipase (LPL), an enzyme that breaks down triglycerides in circulating lipoproteins. Inhibition of LPL by ANGPTL3 leads to increased plasma triglyceride levels. ANGPTL4 also plays a role in lipid metabolism. It is involved in regulating the delivery of triglycerides to tissues for energy storage. ANGPTL4 is often referred to as a fasting-induced adipose factor because its expression is upregulated during fasting. ANGPTL5 is involved in the regulation of triglyceride and glucose metabolism. It has been found to influence insulin sensitivity and lipid storage. ANGPTL6 (also known as betatrophin) has been implicated in regulating lipid and glucose metabolism, and it has garnered interest due to its potential role in beta-cell proliferation in the pancreas, which could have implications for diabetes treatment.

Protein Structure:

• Primary Structure: ANGPTLs typically possess an N-terminal signal peptide, a coiled-coil domain, and a fibrinogen-like domain. The signal peptide facilitates secretion, while the coiled-coil and fibrinogen-like domains are crucial for their function.
• Tertiary Structure: The fibrinogen-like domain is essential for the biological activity of ANGPTLs.
• Quaternary Structure: ANGPTLs can form oligomers, which are important for their stability and function.

Classification and Subtypes:

• ANGPTL1: Involved in inhibiting angiogenesis and promoting vascular integrity.
• ANGPTL2: Associated with inflammation and tissue remodeling.
• ANGPTL3: Plays a crucial role in lipid metabolism by inhibiting lipoprotein lipase (LPL) and endothelial lipase (EL).
• ANGPTL4: Regulates lipid metabolism and is involved in the inhibition of LPL activity.
• ANGPTL5: Less well characterized, with suggested roles in lipid metabolism.
• ANGPTL6 (also known as Angiopoietin-related growth factor): Involved in promoting angiogenesis and metabolic homeostasis.
• ANGPTL7: Suggested roles in ocular physiology and potentially in regulating intraocular pressure.
• ANGPTL8 (also known as Betatrophin): Regulates lipid metabolism and insulin resistance.

Function and Biological Significance:

• Lipid Metabolism: ANGPTLs, particularly ANGPTL3, ANGPTL4, and ANGPTL8, play critical roles in lipid metabolism by modulating the activity of lipases, impacting triglyceride levels and overall lipid homeostasis.
• Angiogenesis: Some ANGPTLs, such as ANGPTL1 and ANGPTL6, can influence blood vessel formation and stability, although they do not directly bind to the Tie2 receptor like angiopoietins.
• Inflammation: ANGPTL2 is involved in chronic inflammation and is linked to various inflammatory diseases, including atherosclerosis and rheumatoid arthritis.
• Energy Homeostasis: ANGPTL8, also known as Betatrophin, is implicated in regulating glucose metabolism and insulin sensitivity.

Interactions:

• Lipoprotein Lipase (LPL): ANGPTL3 and ANGPTL4 inhibit LPL, thereby regulating plasma triglyceride levels.
• Endothelial Lipase (EL): ANGPTL3 also inhibits EL, affecting high-density lipoprotein (HDL) metabolism.
• Other Receptors and Proteins: ANGPTLs may interact with integrins and other surface receptors influencing cellular adhesion, migration, and proliferation.

Clinical Issues:

• Cardiovascular Diseases: Dysregulation of ANGPTLs, particularly ANGPTL3 and ANGPTL4, is associated with lipid disorders and cardiovascular diseases. Elevated levels can lead to hypertriglyceridemia and atherosclerosis.
• Metabolic Disorders: ANGPTL8 has been linked to insulin resistance and type 2 diabetes, making it a potential target for therapeutic intervention.
• Cancer: ANGPTLs, due to their roles in angiogenesis and inflammation, are being studied in the context of cancer progression and metastasis. ANGPTL4, for instance, has been implicated in promoting metastasis in certain cancers.
• Therapeutic Potential: Targeting ANGPTLs offers potential for treating metabolic disorders, cardiovascular diseases, and certain cancers. Inhibitors of ANGPTL3 are being developed to lower triglyceride levels in hyperlipidemic patients.

Summary:

ANGPTLs are a diverse family of proteins that, despite their structural similarity to angiopoietins, function through different mechanisms and receptors. They play significant roles in lipid metabolism, angiogenesis, inflammation, and energy homeostasis. Understanding the specific functions and regulatory mechanisms of ANGPTLs is crucial for developing targeted therapies for a range of diseases, including cardiovascular and metabolic disorders, as well as cancer.