Cardiogen

Cardiogen is the name for the tetrapeptide Ala-Glu-Asp-Arg (AEDR). It is one of a series of short peptides from the St Petersburg Institute of Bioregulation and Gerontology. Epitalon (Ala-Glu-Asp-Gly) and pinealon (Glu-Asp-Arg) are in the same series. The group's own tables pair this sequence with cardiovascular regulation (Khavinson et al., 2021; Khavinson et al., 2022).

The published work on this sequence is very thin. That is the main thing to know before you plan work with it. So this guide is short by design.

So all identity figures above come from two sources: PubChem and the sequence used in the primary papers. The two sources do not conflict. They do not overlap.

Almost nothing is indexed under the product name. A PubMed search for "cardiogen" returns about 80 records. Nearly all are unrelated. Most match Filière Cardiogen. This is a French rare cardiac disease network named in author affiliations. A few concern the CardioGen-82 rubidium generator or cardiogenic shock. Only four concern the peptide. Searching the sequence adds a handful more. That gives a usable total of about ten papers. Most come from the peptide's home institute or its partner groups. Each summary below states the model used.

Explant culture of rat heart tissue

The closest thing to a primary result is organotypic explant work. The same programme set up this method earlier. That work used organ extracts rather than synthetic peptides (Chalisova et al., 2000). One study cultured explants from 3-week-old and 18-month-old rats. The explants came from heart, lung, prostate and pancreas. Four peptides from the series were tested. Each one was reported to stimulate growth of the explant from its matching organ at 0.05 ng/mL (Zakutskii et al., 2006).

A follow-up used myocardium explants from 3-month-old and 24-month-old rats. It compared 20 amino acids with the tetrapeptide at 10⁻¹² M. Seven amino acids stimulated proliferation in tissue from young rats. Only two did so in tissue from old rats. The tetrapeptide was reported to stimulate proliferation in both. Lower p53 expression was also reported on immunohistochemistry (Chalisova et al., 2009).

Cell culture, histone binding and a tumour model

The tetrapeptide was tested in cultured mouse embryonic fibroblasts. It was reported to raise expression of actin, tubulin and vimentin by two to five times. It was also reported to raise lamin A and lamin C expression by two to three times (Khavinson et al., 2012). Aging human prostate fibroblast cultures were also tested.

There, it was one of three short peptides reported to raise expression of differentiation markers. Peptide T-38 was the most active (Kheifets et al., 2010). Across the series, the proposed mechanism is sequence-selective binding to DNA and histones. That proposed mechanism does not involve a cell-surface receptor.

No receptor has been reported. In fluorescence-quenching assays, six short peptides, this one included, bound labeled wheat histones. Binding depended on the histone, the peptide and oligonucleotide methylation state (Fedoreyeva et al., 2013). Docking work placed this peptide among the stronger binders at the LAT1, LAT2 and PEPT1 transporter sites (Khavinson et al., 2023).

In rats carrying transplanted M-1 sarcoma, tumour cell apoptosis was reported above control levels. Tumour growth was also reported to be inhibited in a concentration-related way. The authors attributed this to haemorrhagic necrosis and the tumour vascular network, not a direct cytostatic action (Levdik and Knyazkin, 2009).

A cardiac claim that is not indexed

A 2022 review states that mass spectrometry found the tetrapeptide in a heart polypeptide complex. It also summarises a rat coronary-ligation model with about threefold lower mortality than control. In that model, the review notes smaller necrotic zones and preserved myocardial glycogen (Khavinson et al., 2022). That is a secondary account. The primary report is not indexed in PubMed under the product name or the sequence. So it could not be verified here.