B7-33

The heart has been the most heavily studied target for B7-33. In a model of ischemia-reperfusion injury — the kind of damage that occurs when blood flow is restored to heart tissue after a heart attack — B7-33 cut infarct size roughly in half (about 22% versus 45% in untreated controls) and preserved heart function measured by fractional shortening (1). The benefit persisted for at least a week after the initial injury, suggesting B7-33 doesn't just blunt acute damage but shapes how the heart remodels in the days that follow.

The protective mechanism appears to work through ERK1/2 signaling, a pathway involved in cell survival, and through reducing endoplasmic reticulum stress — a form of cellular distress that drives heart muscle cells to die after injury (1). In heart muscle cells exposed to simulated ischemia, B7-33 improved survival and lowered levels of GRP78, a marker of this stress response.

In a separate cardiomyopathy model where the heart had been damaged by isoprenaline, B7-33 matched the parent relaxin hormone in reducing left ventricular fibrosis, normalizing inflammation, reversing cardiomyocyte enlargement, and restoring blood vessel density — and it outperformed perindopril, a frontline ACE inhibitor, on fibrosis reduction specifically (2). The anti-fibrotic effect appeared faster than what perindopril produced, which is notable because scar reversal is generally one of the harder problems in cardiac medicine.

Fibrosis — the buildup of stiff scar tissue that replaces healthy functional tissue — is the central problem B7-33 was developed to address. The peptide binds RXFP1 on fibroblasts, the cells responsible for laying down scar tissue, and pushes them toward a quiescent (inactive) state rather than letting them continue producing collagen (3, 4).

In fibroblasts that natively express RXFP1, B7-33 shows potency equivalent to the full relaxin hormone, even though it appears weaker in artificial cell systems where the receptor is overexpressed (3). This is an important distinction — it means B7-33 works well in the tissue contexts that actually matter, even if standard receptor-binding assays underestimate its activity.

The anti-fibrotic effect has been confirmed across multiple organs and disease models. In one creative application, B7-33 was loaded into biodegradable polymer coatings on implanted materials; the slow release of peptide reduced the thickness of fibrous capsules forming around the implant by roughly 49% over six weeks (5). In a cancer context, B7-33 incorporated into targeted nanovesicles reduced both fibrotic matrix deposition and tumor blood vessel density in cholangiocarcinoma models, achieving roughly 68% tumor growth inhibition by reshaping the tumor's stromal environment (6).

Beyond fibrosis, B7-33 reproduces several of relaxin's effects on blood vessel function. A single injection enhanced bradykinin-mediated relaxation in mesenteric arteries by boosting endothelium-derived hyperpolarization, a key mechanism by which the inner lining of blood vessels signals smooth muscle to relax (7). The effect was equivalent to that of serelaxin, the recombinant full-length relaxin used in clinical heart failure research, at equimolar doses.

In a model of preeclampsia-related endothelial dysfunction — where arteries are exposed to factors released by distressed placental tissue — co-incubation with B7-33 prevented the dysfunction from developing (7). Given that preeclampsia is fundamentally a disease of vascular dysfunction during pregnancy, and that relaxin is naturally elevated in pregnancy, this line of research connects directly to the peptide's biological origins.

A recurring challenge with B7-33 is its short half-life in serum — roughly six minutes in laboratory conditions — which limits how it can be used (8). Several approaches have been developed to extend its activity. Fatty-acid conjugation (lipidation) at appropriate positions extended in vitro half-life roughly tenfold, from about 6 minutes to 60 minutes, by allowing the peptide to bind serum albumin and circulate longer (8).

A more recent strategy used glycine-functionalized iron oxide nanoparticles to deliver B7-33 orally — overcoming the usual problem that peptides are destroyed in the digestive tract before they can reach circulation (9). When given by mouth every 72 hours over four weeks, the nanoparticle-delivered B7-33 produced greater anti-fibrotic effects on heart tissue than perindopril. The mechanism appears to involve uptake by immune cells (dendritic cells) that then transport the peptide systemically. If this approach holds up, it would substantially expand how relaxin-mimetic peptides could be administered.

The published research on B7-33 has not reported significant adverse effects in the laboratory and preclinical work conducted to date. The peptide appears well-tolerated across the various delivery methods that have been tested — direct injection, slow-release coatings, nanoparticle conjugates, and oral nanoparticle formulations.

The body of B7-33 evidence comes primarily from preclinical and laboratory work, with no published human clinical data available so far. Long-term safety in people has not been characterized. Because B7-33 acts on the relaxin receptor system, which has wide tissue distribution and roles in reproductive and vascular physiology, effects in humans across longer timeframes remain an open question that will require formal clinical study to resolve.