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Written By: Sponsored | Published : May 22, 2023 6:13 PM IST
Tissues are considered to become abnormally thick or deteriorate in subjects experiencing "fibrosis". A severe chronic illness's "end stage" is often characterized by fibrosis. While there is no one-size-fits-all approach to managing fibrosis, a protein called H2-relaxin seemed to researchers to reduce severe, long-term scarring of cardiac tissues due to heart damage in a clinical trial conducted in 2012. [vi] H2-relaxin is an endogenous protein, and its synthetic counterpart is the B7-33 peptide. In addition to the properties listed below, B7-33 may also have anti-fibrotic qualities, much like H2-relaxin, as suggested by research.
Including relaxin, H3-relaxin, insulin-like peptide-3, and insulin-like peptide-5, the H2-relaxin protein family includes a wide variety of hormones and neurotransmitters. It has been hypothesized that these proteins may have different biological impacts on the reproductive, musculoskeletal, and cardiovascular systems. [ii]
Research suggests these relaxin proteins may bind to four receptors: RXFP-1, RXFP-2, RXFP-3, and RXFP-4.
Single-chain peptide B7-33 is a simplified analog of the naturally occurring protein relaxin 3. Four subunits comprise the relaxin peptide: the signal peptide, the B chain, the C chain, and the COOH terminus. Initial attempts to duplicate these peptide structures yielded exceedingly insoluble and inert peptides; thus, the investigations were abandoned. After years of study, scientists extended the COOH terminus on the peptide and synthesized a B chain, creating the first apparently soluble counterpart, the B7-33 peptide, in 2016. [iii]
Studies suggest the peptide differs from endogenous proteins structurally, and in other ways. The cAMP pathway may not be the target of the B7-33 peptide's actions. It is hypothesized by researchers that activating the cAMP system H2-relaxin may produce anti-fibrotic potential, promoting tumor development. This is a serious problem that may arise from relaxin. Research [i] suggests the peptide may have a high affinity for the RXFP-1 receptors. Increased production of MMP-2 matrix metalloproteinase molecules seems to result from the peptide binding with RXFP-1 receptors and stimulating the pERK pathway. Studies speculate these compounds may then prevent fibrosis by reducing tissue scarring. [i]
Natural H2 relaxin was hypothesized to be a vasoprotective agent because of its proposed actions against heart failure and fibrosis. However, due to the high cost and effort required to produce H2 relaxin exogenously, it became more important to investigate the possibility that its analog, B7-33 peptide, might exhibit similar action.
In a 2017 research [iv], male Wistar rats were given either sodium acetate (serving as a placebo), H2 relaxin, or B7-33 peptide into their tails. Three hours after, the mesenteric artery, renal artery, and abdominal aorta of the mice were analyzed for their vascular functioning. B7-33 and H2 relaxin seemed to have better vasodilatory capabilities in the mesenteric artery, while findings were less encouraging in the renal and abdominal aorta.
Another investigation [iv] was conducted on female mice with endothelial dysfunction produced artificially to investigate this phenomenon further. Mice were given either B7-33 or H2 relaxin after that. Following this, the researchers hypothesized that both compounds apparently contributed to stopping the progression of endothelial dysfunction in the mice. These findings suggest that B7-33 may prevent additional damage to blood vessels by possibly mimicking H2 relaxin's vasoprotective actions.
Increased maternal hypertension and reduced fetal weight describe the pregnancy disorder known as preeclampsia. This research [v] aimed to investigate the potential of the B7-33 peptide in mitigating preeclampsia in pregnant test subjects.
Cytotrophoblasts (CTBs) were employed in cell culture for this in vitro research. The innermost layer of the embryo's cells is called cytotrophoblasts. These cells were given either a placebo, steroid, or glucose; some were given marinobufagenin. Following this, a subset of the cells was subjected to a relaxin antagonist. The B7-33 compound was subsequently added to all of the cells. Upon closer inspection, cells interacting with the B7-33 peptide were speculated to have increased vascular endothelial growth factor (VEGF) levels. In cells given relaxin antagonists, VEGF levels appeared to drop. These findings support the hypothesis that the peptide may possibly mitigate the harmful action of hyperglycemia and marinobufagenin in preeclampsia.
H2 relaxin is considered to be a naturally occurring protein that inhibits scar tissue formation. The cAMP pathway is crucial to their operation. Full-length H2 relaxin protein, as suggested in studies (6, 7), has been posited to raise heart rate and promote the spread of cancerous cells. It may work via stimulating the cAMP pathway, and this pathway may be responsible for this action. Therefore, scientists sought a derivative that could mimic its anti-fibrosis biological potential without cAMP activation. Reports suggest that when the peptide was given to animals with myocardial infarction, heart tissue fibrosis appeared to be reduced by about 50%. Matrix metalloproteinase protein concentration was suggested to have been elevated due to the peptide.
In addition, mice with prostate cancer were used in research [i]. These mice were either given B7-33 (generally provided to exhibit potential anti-fibrosis action) or more B7-33 (without any hypothesized benefits). Interestingly, the results were identical in both cases, namely, blocking the fibrosis progression. This suggested that cAMP activation may not be the mechanism via which the peptide worked.
Typically, the body may reject foreign objects by completely isolating them via a process called fibrosis so that they can't cause any problems. This may be helpful in the case of antigens and disease-causing substances. Or, it might be problematic when implanting a cardiac stent, which the body may see as a foreign invader and attempt to eliminate.
A device coated with the peptide was put into the animals in one of the trials [vii] to potentially reduce fibrosis. Studies suggest that throughout the study's 6-week duration, releasing these peptides from the coating appeared to reduce the device thickness loss (caused by fibrosis) by 49.2%. Though preliminary, the findings held hope for further research on the peptide.
More investigation is required to prove its potential in scientific research, and these studies must continue. Only academic and scientific institutions can use B7-33 peptides. If you are a licensed professional interested in purchasing B7-33 peptides for your clinical studies, visit Core Peptides. Please note that none of the items listed are approved for human or animal consumption. Laboratory research chemicals are only for in-vitro and in-lab use. Any kind of physical introduction is illegal. Only authorized academics and working professionals may make purchases. The content of this article is intended only for instructional purposes.
Use Disclaimer: (Above mentioned article is consumer connect initiative. This article is a paid publication and does not have journalistic/editorial involvement of IDPL, and IDPL claims no responsibility whatsoever)
References
[i] Mohammed Akhter Hossain et al, A single-chain derivative of the relaxin hormone is a functionally selective agonist of the G protein-coupled receptor, RXFP1, Drug Discovery Biology Pharmacology Monash Biomedicine Discovery Institute, Vol 7, 2016. https://research.monash.edu/en/publications/a-single-chain-derivative-of-the-relaxin-hormone-is-a-functionall
[ii] R J Summers, Recent progress in the understanding of relaxin family peptides and their receptors, British Journal of Pharmacology, Vol 174, issue 10, pg 915-920. https://doi.org/10.1111/bph.13778
[iii] Nitin A Patil et al, Relaxin family peptides: structure activity relationship studies, British Pharmacological Society, vol 174 issue 10, published 06 December 2016. https://doi.org/10.1111/bph.13684
[iv] Marshall SA, O'Sullivan K, Ng HH, Bathgate RAD, Parry LJ, Hossain MA, Leo CH. B7-33 replicates the vasoprotective functions of human relaxin-2 (serelaxin). Eur J Pharmacol. 2017 Jul 15;807:190-197. doi: 10.1016/j.ejphar.2017.05.005. Epub 2017 May 3. PMID: 28478069. https://pubmed.ncbi.nlm.nih.gov/28478069/
[v] S.H Afroze et al, Abstract P3042: Novel Peptide B7-33 and It's Lipidated Derivative Protect Cytotrophoblasts From Preeclampsia Phenotype in a Cellular Model of the Syndrome, 4 Sep 2019. https://doi.org/10.1161/hyp.74.suppl_1.P3042
[vi] Silvertown JD, Ng J, Sato T, Summerlee AJ, Medin JA. H2 relaxin overexpression increases in vivo prostate xenograft tumor growth and angiogenesis. Int J Cancer. 2006 Jan 1;118(1):62-73. https://pubmed.ncbi.nlm.nih.gov/16049981
[vii] N.Welch et al, Coatings Releasing the Relaxin Peptide Analogue B7-33 Reduce Fibrotic Encapsulation, ACS Applied Materials and Interfaces, Nov 2019. https://www.researchgate.net/publication/337205944_Coatings_Releasing_the_Relaxin_Peptide_Analogue_B7-33_Reduce_Fibrotic_Encapsulation
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