Vesugen

Vesugen (KED) is a synthetic tripeptide bioregulator consisting of lysine, glutamic acid, and aspartic acid (Lys-Glu-Asp), developed by Dr. Vladimir Khavinson for vascular health. Research demonstrates its ability to increase microvascular density in aged animals by 2.5-2.8 times and normalize endothelial cell function through epigenetic regulation of gene expression. Clinical studies in elderly patients show effectiveness in treating atherosclerosis, improving microcirculation, and protecting blood vessels from age-related dysfunction. The peptide acts as a geroprotector with vasoprotective properties, regulating expression of key proteins including Ki-67, SIRT1, endothelin-1, and connexin-37.

Vascular Health and Microcirculation

Vesugen significantly improves microvascular density and function in aging. Animal studies demonstrate that vascular peptide bioregulator treatment increased microvasculature density in the pial tunic of old rats (22-24 months) by 2.5-2.8 times compared to age-matched controls ^[1][12][13]. In hypertensive rats, microvascular network density increased by approximately 1.7 times after treatment ^[13][15]. The peptide also improved tissue perfusion levels by ~15% and increased oxygen saturation in brain cortex microvessels ^[12][15].

Atherosclerosis and Cardiovascular Protection

Clinical studies established effectiveness in treating atherosclerosis of the heart, brain, and lower extremity vessels ^[1][5]. The peptide normalized endothelin-1 expression, which increases during atherosclerosis and restenosis, providing vasoprotective effects in elderly patients ^[6][7]. In a clinical trial of 41 patients with vasculogenic erectile dysfunction as a manifestation of atherosclerosis, the vasoactive tripeptide Vesugen produced measurable improvements in penile arterial blood flow ^[2].

Endothelial Cell Function and Proliferation

Vesugen stimulates proliferation-associated protein Ki-67 that decreases during aging in vascular endothelial cell cultures from both young and old animals ^[1]. The vasoprotective effect is realized through epigenetic regulation of Ki-67 gene expression ^[1]. The peptide interacts with the promoter region of the MKI67 gene, specifically contacting the core promoter located from -14 to +12 base pairs relative to the transcriptional initiation site ^[1]. Studies show KED peptide prevents endothelial cell apoptosis and increases endothelial cell proliferation ^[4].

Gene Expression and Epigenetic Regulation

The KED peptide regulates expression of multiple genes involved in aging and cellular function. It increased expression of IGF1 by 3.5-5.6 fold and TERT by eightfold in aging mesenchymal stem cell cultures ^[10]. The peptide decreased expression of FOXO1 by 1.6-2.3 fold and enhanced NFκB gene expression ^[10]. The geroprotective effect occurs through increasing SIRT1 expression, which participates in DNA repair ^[6]. KED peptide also regulates genes of cell aging and apoptosis (p16, p21) and neuronal differentiation markers ^[8].

Anti-Aging and Geroprotective Effects

In a clinical study of 32 people aged 41-83 years with polymorbidity and organic brain syndrome, Vesugen demonstrated significant anabolic effects and improved central nervous system activity ^[3]. The preparation showed more visible geroprotective effects than the comparator peptide Pinealon, slowing the rate of aging by biological age indicators ^[3]. In oral stem cells, KED peptide decreased p16 and p21 mRNA expression (senescence markers) by 1.82-3.23 times compared to controls ^[14].

Neuroprotective Properties

Daily administration of KED peptide at 400 μg/kg in Alzheimer's disease mouse models tended to increase neuroplasticity and prevented dendritic spine loss ^[4]. In hippocampal neuron cultures under amyloid synaptotoxicity conditions, KED peptide increased the number of mushroom spines by 20% ^[9]. The peptide regulates expression of genes associated with Alzheimer's pathogenesis including SUMO, APOE, and IGF1 ^[8]. Oral application of KED improved memory and attention in elderly individuals with functional CNS issues ^[8].

Signal Molecule Regulation

Vesugen influences production of several important proteins in the endothelium, including SIRT1, endothelin-1, connexin, Ki67, Cx43, VEGF, and p53 ^[1][6]. The peptide normalized connexin-37 expression and restored cellular communication ^[6]. Studies suggest connexin-37 and endothelin-1 can serve as predictive markers for prognosis of post-stenting complications in atherosclerotic patients ^[7].

Clinical Safety Profile

Vesugen has been studied in multiple clinical trials in elderly patients with generally favorable safety outcomes. A study of 32 people aged 41-83 years with chronic polymorbidity found the peptide to be safe at the genetic level, with recommendations for use as a neuroprotective geroprotector ^[3]. Clinical studies established its use in treating atherosclerosis, microcirculation problems, and psycho-emotional stress, as well as for prevention of vascular diseases in elderly people ^[1][5].

Adverse Effects and Concerns

In the polymorbidity study, researchers noted some concerning findings: prooxidant activity was detected through chemiluminescence analysis, and there was a significant decrease of CD34+ positive hematopoietic polypotent cells in blood, indicating potential inhibition of hematopoiesis ^[3]. These findings warrant further investigation and monitoring in clinical applications.

Research Quality and Limitations

Most peer-reviewed research on Vesugen has been published in Russian journals, particularly "Advances in Gerontology" and "Bulletin of Experimental Biology and Medicine," with limited Western clinical trials. Many studies are published in Russian with English abstracts available. The research primarily originates from the St. Petersburg Institute of Bioregulation and Gerontology and affiliated Russian institutions ^{[1][2][3][5][6][12][13][14][15]}. While animal studies show consistent positive effects, larger randomized controlled trials in diverse populations are needed.

Dosing and Administration

Animal studies used doses of 400 μg/kg administered intraperitoneally daily for 2-4 months ^[4]. Clinical formulations are available as oral supplements and injectable forms. The peptide is marketed under various trade names including "Slavinorm" in research studies ^[12][13][15]. Specific human dosing protocols are not clearly established in the peer-reviewed literature.

Contraindications and Precautions

Given the observed effects on hematopoiesis markers ^[3], caution may be warranted in patients with blood disorders or bone marrow dysfunction. The prooxidant activity observed in one study ^[3] suggests potential need for monitoring oxidative stress markers during treatment. No specific contraindications have been established in published research. As with all experimental peptides, use should be under medical supervision with appropriate monitoring.