B7-33 is a single-chain peptide. It is derived from a naturally occurring compound called H2-Relaxin. Relaxin proteins are a family of four proteins comprising of Relaxin, Insulin-like peptide 3, H3-relaxin, and insulin-like peptide 5. They all possess pleiotropic actions impacting the cardiovascular system, musculoskeletal system, reproduction system, etc. These proteins perform these actions through four types of receptors, namely RXFP1/2 and RXFP3/4. Various ligands, such as cAMP and corticotropin-releasing hormone, stimulate these receptors. All these agonists can express antioxidant, anti-inflammatory, and wound healing properties. However, Relaxin, in addition to possessing above mentioned properties, also exhibits antihypertrophic, vasodilator, and angiogenic properties. This is why Relaxin and its derivatives have been of great interest for researchers to explore its further benefits.


B7-33 Specifications:

PubChem CID: 318164840
Synonyms: (B7-33) H2, GTPL9321


Mechanism of action

An important property of the B7-33 peptide that helps it exceed its potential compared to the naturally occurring Relaxin protein is its ability to preferentially act through the pERK Pathway instead of the cAMP-mediated pathway. Also, it has a greater affinity to bind to RXFP1 receptors than Relaxin. However, the antifibrotic properties are mediated through RXFP1-angiotensin II type 2 receptors stimulation. It further activates the pERK1/2 pathway, leading to enhanced production of Matrix Metalloproteinase (MMP)-2. These collagen degrading proteins play their role in controlling fibrosis and eventually preventing scarring. This property of B7-33 acts through pERK1/2 without activating the cAMP pathway. This is significantly important because studies have indicated cAMP to have a tumor-promoting potential which is the most dreadful side effect associated with the full-sequence Relaxin. Another advantage of B7-33 over H2-relaxin protein is its less complicated structure. It makes it less laborious to produce it in the laboratories while still retaining all the useful properties associated with the native Relaxin proteins. This ease of production implies a lower cost of manufacturing as well.


Research implications of B7-33

1. Antifibrotic Properties:
Fibrosis or scarring is an unwanted side-effect of healing following an injury which is more significant in chronic inflammatory diseases. Fibrosis in the chronic diseases of the liver, heart, or lungs is the leading cause of organ failure. If only we could control this unorganized tissue regeneration, we could prevent organ failure. A study on H2-relaxin proteins indicated their potential in reducing fibrosis following an ischemic injury to the heart. It demonstrated an immediate vasodilatory effect in the heart that led to a reduction in the long-term scarring.

Though it was the first product that got approved for the treatment of Acute Heart Failure, it wasn’t an ideal therapeutic agent owing to its tumor-promoting side effect. And it could only be given by intravenous route. Studies have indicated that the use of B7-33 produces a similar yet more pronounced reduction in fibrosis without activation of the cAMP pathway avoiding the risk of tumors. A study performed on rat models demonstrated that the use of B7-33 led to a reduction in scarring by approximately 50% following an injury. This reduction in fibrosis eventually leads to improved cardiac function with lesser long-term complications associated with heart failure.

2. Blood vessel protection and use in Preeclampsia:
Researchers have indicated that B7-33 possesses vasoprotective properties of Human Relaxin-2 (Serelaxin) against long-term scarring and endothelial dysfunction. It appears to do this through activation of bradykinin-mediated relaxation of arteries that is endothelium-dependent. B7-33 is more selective in its action as compared to Serelaxin and is cheaper as well.

Preeclampsia is a common complication of pregnancy that can prove life-threatening to the mother and the fetus. It leads to high blood pressure in the mother and reduced fetal weight. A recent study provides evidence that B7-33, by stimulating RXFP-1 receptors, leads to enhanced Vascular Endothelial Growth Factor (VEGF) production. VEGF stimulates the production of the cytotrophoblast cells in the fetus, which are responsible for developing blood flow from mother to baby. B7-33 can help improve the fetus’s survival by prolonging the duration of pregnancy in cases where an early delivery of the baby is suggested.

3. Exogenous Implants:
Exogenous-implanted medical devices often fail to perform their function in full efficacy because the body reacts to it as a foreign object and walls it off by stimulating fibrosis around it. This is particularly harmful in cardiac stenting, where fibrosis can lead to implant dysfunction. Experiments have proved that fibrosis is significantly reduced after coating the implant with B7-33, which improves implant efficacy.


Disclaimer: The products mentioned are not for human or animal consumption. All the information shared in this article is for educational purposes only.

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