B7-33 and its Potential as an Anti-fibrotic

by | Jun 27, 2022 | Research

B7-33 is the synthetic derivative of Human H2-relaxin. B7-33 acts similarly to h2-relaxin but does not increase the production of cAMP. Its functions are evident in the reduced fibrosis in chronic and acute diseases, such as lung inflammation, heart failure, kidney, etc. B7-33 also acts to reduce scar formation seen in cardiac injuries. Scientists believe it may be a vital ancillary to the arsenal for fighting against certain vascular disorders such as preeclampsia during pregnancy.

 

Description of B7-33

B7-33 is a soluble produced single-chain peptide equivalent of the naturally occurring protein H2-relaxin. B7-33 contains properties similar to human h2-relaxin without increasing the production of cAMP. B7-33 peptide functions to activate ERK1/2 phosphorylation, improve matrix metalloproteinase 2 (MMP2) expression, and extracellular collagen degradation.

 

The Functions/Importance of B7-33

Despite having a strong affinity for the RXFP-1 receptor, it doesn’t activate the cAMP pathway. Instead, it activates the pERK pathway—a pathway known for inhibiting the cell cycle in the G1 phase and is affected in health conditions like Alzheimer’s disease and Crutzfeld-Jacob disease.

The inhibition of the cell cycle progression in RXFP-1 receptor cells by the ompound will cause several effects. The anti-fibrotic property of B7-33 enhances the pERK1/2 signaling—boosting the synthesis of the enzyme matrix metalloproteinase (MMP)-2, which breaks down collagen. It is of great advantage that B7-33 does not activate cAMP because cAMP activation may modulate some tumor-promoting effects.

 

1. Producing the Peptide is Simple:

B7-33 is more advantageous than the natural H2-relaxin protein because it does not activate the cAMP pathway but still holds onto its anti-fibrotic feature. This is one of its advantages as B7-33 production is easy because it has less intricate 2D and 3D structures.

 

2. The Anti-fibrotic Function of B7-33:

Fibrosis is scarring or the unorganized regeneration of tissues. It is the last stage of several chronic diseases ranging from cardiovascular to lung diseases to cirrhosis of the liver and aberrant wound healing. Fibrosis is considered the primary cause of organ failure. According to clinical studies, the administration of H2-relaxin following fibrosis leads to vasodilatory effects and a reduction in the long-term scarring effect of heart damage. That notwithstanding, H2-relaxin has some setbacks, such as difficulty in production and administration via injection only. It increases heart rate and may increase cancer progression. Most of these adverse effects are due to the activation of the cAMP pathway, allowing for the research on B7-33.
According to research by Dr. Akhter Hossain, one of the lead developers of B7-33, it increases MMP-2 production slightly better than H2-relaxin. The results show a massive decrease in cardiac fibrosis in rat models with MI-induced heart failure. Subsequently, it improved heart function and reduced long-term symptoms such as heart failure complications. Research shows that B7-33 reduces scarring in the heart following injury by about 50%. Similar results are evident in mouse models with asthma and lung fibrosis.
Scientists administered B7-33 in mouse models with prostate cancer, and B7-33 did not promote tumor growth at doses required for treating fibrosis. It also did not induce tumor growth when the dosage increased above normal. This is possible because B7-33 functions via the pERK pathway and does not activate cAMP.

 

3. The Protection of Blood Vessels:

Clinical research in male Wistar rats proves that the compound exhibits the vasoprotective effects of serelaxin by promoting bradykinin-mediated endothelium-dependent relaxation in arteries. It does this by increasing endothelium-derived hyperpolarization in vascular beds. The ability of B7-33 to cause vasorelaxation may make it a vital ancillary for treating certain cardiovascular conditions, including preeclampsia during pregnancy.

 

4. The Role of B7-33 in Preeclampsia:

Preeclampsia, termed Toxemia, is a critical pregnancy condition characterized by high blood pressure and decreased fetal weight. Preeclampsia is complex. In some cases, it may be life-threatening to both the fetus and the mother. In extreme cases, immediate delivery of the baby is opted for, thereby, a common cause of premature delivery. Studies show that B7-33 can help control preeclampsia in severe cases.
In this research, B7-33 acts like an RXFP-1 receptor to boost VEGF production in cytotrophoblasts—cells found in the developing fetus that help stimulate blood flow between mother and baby. Therefore, by stimulating VEGF production, B7-33 enhances blood vessel growth—improving the blood supply between the child and mother.
Research has it that lipidated B7-33 in vivo has a longer half-life making it a more potent therapy—enhancing the odds that enteral administration can amount to plasma levels of the therapeutic peptide.

 

5. Incorporating B7-33 into Anti-Fibrotic Materials:

The human body fights foreign bodies by removing them completely. If impossible, the body will start walling off the foreign bodies by fibrosis—isolating them from the body and reducing their ability to cause harm—disease, mutations, and dysfunctions. It becomes an issue when one opts for an implant. In this case, fibrosis causes dysfunction or implant degradation, artery occlusion, reduced blood supply, and heart attack.
B7-33 offers a safe implant coating. Scientific studies show that coating from B7-33 reduced the thickness of fibrotic capsules by about 50% in six weeks. Putting B7-33 into use may prevent the use of systemic drugs to decrease the fibrosis of implanted medical devices—allowing for safe device implant even in a wide range of patients (e.g., patients with severer conditions).

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