BPC-157 therapy in the cardiovascular system. The heart-protecting effect of the peptide and its use in cases of metabolic diseases.

Abstract: The BPC-157 peptide, demonstrating a broad spectrum of action, is also used in the proper functioning of the cardiovascular system. Peptide therapy helps alleviate symptoms of circulatory system diseases or completely eliminate them. The prophylactic profile of BPC-157 allows it to be defined as a substance with cardioprotective effects.

Keywords: cardiovascular system; treatment; BPC-157 therapy; heart; blood vessels; capillaries; artery; vein; circulatory system diseases; plasma; erythrocytes; leukocytes; blood; oxygen; transport; functions; diabetes; coronary artery disease; hypertension; varicose veins; atherosclerosis; concentration; dose; vasodilation; cardioprotection;

List of abbreviations: ACE - angiotensin-converting enzyme inhibitors; ACh - Acetylcholine; ARB - angiotensin receptor blockers; BPC - Body Protection Compound; ChUK - prevention of circulatory system diseases; PE - polyethylene;

Material and methods of research: Studies conducted on laboratory animals, rats, males and females. BPC-157 therapy in the cardiovascular system. Cardioprotective action of the peptide and its application in metabolic diseases.  

Cardiovascular system

Structure of the cardiovascular system The cardiovascular system, also called the circulatory system, consists of elements such as the heart, veins, arteries, and capillary blood vessels. Due to its extensive structure, the circulatory system forms a complex, closed system performing specific functions. Additionally, the cardiovascular system includes the blood itself, which contains plasma, erythrocytes, and leukocytes. The diagram of the circulatory system's structure will allow us to visually recall its components and facilitate understanding of the influence of the peptide BPC-157 on their individual functions.

Functions of the cardiovascular system

The exact outline of the circulatory system's functions is well known to everyone, so its presentation will be typically in the form of a reminder. The circulatory system as a whole is responsible for transporting the most important and essential substances in our body, including oxygen and nutrients. Individual elements of the system perform specific functions. The heart, being the main organ of the entire circulatory system, functions as a pump that continuously circulates blood throughout the body. Arteries allow blood to be carried away from the heart and transported to all tissues in our body. Veins, on the other hand, return blood back to the heart. Capillaries allow the exchange of important substances, such as oxygen, with the surrounding tissues. Other functions of the circulatory system include hormone transport, protection against microorganisms, body thermoregulation, and control of pH levels in the body.  

Cardiovascular diseases influenced by BPC-157 therapy

Cardiovascular diseases are currently among the most common and serious diseases we encounter. The problem is so serious that the symptoms present indicate an already ongoing disease state in the case of circulatory system pathologies. Society is not fully aware, does not take advantage of the possibility of undergoing tests for cardiovascular diseases (ChUK) nor the possibility of preventive therapies that would allow eliminating or minimizing the risk of cardiovascular diseases or their symptoms. Cardiovascular diseases most often occur not only in people who lead an unhealthy lifestyle (poor diet, smoking, alcohol abuse) or avoid physical activity but also in those where it is related to genetics and inheritance, age (older people are more prone to circulatory system disorders), psychological factors, or glucose tolerance disorders. So far, beneficial health effects have occurred with lifestyle changes. Currently, as an innovative method in the prevention and treatment of cardiovascular diseases or disorders, therapy with the peptide BPC-157 is used. The peptide's effect on this system is supported by research and evidence showing that systematic and regular use of BPC-157 positively affects this system. In the form of a table, we present some of the cardiovascular diseases on which BPC-157 has a therapeutic effect. (Tab.1)  

  Table 1. Presentation of selected cardiovascular diseases  

Therapeutic BPC-157 treatment for selected cardiovascular diseases in relation to conducted studies

1. Hypertension

Arterial hypertension is one of the more serious cardiovascular diseases, diagnosed in an increasing number of people. This disorder is classified as the leading cause of death worldwide because abnormal blood pressure values ultimately lead to other cardiovascular diseases. Arterial hypertension manifests as shortness of breath, headaches, insomnia, heart palpitations, hot flashes, or sweating. Preventing the development of arterial hypertension as a primary prevention method through lifestyle changes including diet and starting physical activity can significantly reduce the occurrence of cardiovascular diseases. In the case of people who have no influence on the development of the disease from this group, i.e., those with a family history, diabetes, kidney disease, or those who have reached a certain age, therapy can be applied aimed at limiting and alleviating disease symptoms.  

a. BPC-157 Therapy

The discovery that the peptide BPC-157 exhibits an effect leading to vasodilation means it is used in the treatment of arterial hypertension. Long-term and regular use of the peptide reduces pain symptoms and improves proper blood flow. (Fig.2) BPC-157 therapy also supports protective effects that prevent the occurrence of high blood pressure safely, without side effects. Even at high doses, the peptide does not show adverse effects.

b. Conducted experimental studies

Study 1

Material

The study was conducted on adult female rats weighing from 250g to 300g.

Course of the study

Female rats were euthanized by injection of sodium pentobarbital. Then the abdominal aorta of the rats was isolated, cut into rings 4–5 mm wide, and stored at a temperature of 37°C in a solution containing NaCl, KCl, MgSO4, NaHCO3, KH2PO4, CaCl2, and dextrose. PE and ACh from plasma were used to induce contraction and relaxation of the vessels, respectively. Each ring was then rinsed and the solution concentration was equalized again. After reaching the appropriate concentration in specified doses, from 0.1 to 100 μg/mL, BPC-157 was administered. The degree of vasodilation of the vessels under the influence of the peptide was observed.   Results BPC-157 caused vasodilation in aortic rings with intact endothelium depending on the concentration used. Vasodilation at BPC-157 concentrations of 0.1 or 1 μg/mL ranged from 16.5±5.5% to 19.5±3.0%, at 10 μg/mL 28.3±3.5%, and at a dose of 100 μg/mL 48.3±3.2%. Additionally, vasodilation due to BPC-157 was durable, consistently maintained, and rapidly achieved.   Conclusions The peptide BPC-157 at appropriate concentrations allows for achieving a vasodilation effect, which involves the relaxation of smooth muscles in the walls of blood vessels. The result of this process is the widening of the vessel lumen and a decrease in blood pressure. It can therefore be confidently stated that BPC-157 is a substance supporting the treatment of hypertension. 

2.Thrombosis

Thrombosis is a pathological phenomenon of the circulatory system, manifested by the formation of a thrombus in the deep veins under the deep fascia. This term may include thrombosis in the iliac and perforating veins. Factors responsible for thrombosis include, among others, vessel wall damage or slowed blood flow. In the case of thrombosis, rapid diagnosis and prompt initiation of anticoagulant treatment are essential. Accompanying symptoms of this condition include local pain, swelling of the lower leg or entire limb, skin redness, as well as Homan's sign, where there is calf pain during dorsiflexion of the foot. Treatment of thrombosis involves the fastest possible cessation of the clot, which can lead to further, more dangerous complications, through the administration of anticoagulant drugs. The latest research results show the beneficial effects of BPC-157 during the treatment and prevention of thrombotic disease.  

a. BPC-157 Therapy

In a healthy circulatory system, blood flows freely through veins to the heart. Each element of the blood transport mechanism to the heart, when failing, sequentially causes blood stasis in the veins, the development of inflammation, damage to the endothelial layer lining the vessel, subsequently forming a thrombus that prevents blood transport to the heart. Symptoms of the disease can be alleviated through therapy with the peptide BPC-157, which, as is already known, eliminates inflammation and reduces blood pressure. Acting prophylactically, BPC-157 prevents the development of hyperemia and venous insufficiency, becoming a new precursor in the treatment of thrombotic disease. 

b. Conducted experimental studies

Study 2

Material

The study was conducted on young male albino rats weighing around 200g.

Course of the study

The rats were deeply anesthetized intraperitoneally with thiopental and diazepam. A procedure was performed to completely close the end of the superior mesenteric vein by ligation. This led to a permanent change in blood flow. After the procedure, the peptide BPC-157 was administered at doses of 10 µg/kg and 10 ng/kg. The control group did not receive the peptide dose, receiving saline instead. The assessment of changes was based on the dilation and hyperemia of blood vessels in the heart muscle and arteries. A score of 1 indicates their presence, while 0 indicates their absence. 

Results

Administration of BPC-157 at both doses causes the maintenance of normal parameters within blood vessels compared to the control group, where congestion and venous insufficiency were visible. In the control group of rats, obstruction of the superior mesenteric vein was also observed, where peripheral and central thrombosis quickly appeared. The largest clot appeared in the portal vein, followed by the inferior vena cava. Such symptoms were not observed in the groups that received the BPC-157 peptide. 

Conclusions

The beneficial effect of BPC-157 therapy quickly alleviates and eliminates the consequences associated with thrombosis as well as thrombosis itself. Long-term and systematic use of the peptide leads to the elimination of thrombosis formation and its components. 

3.Hyperkalemia

Hyperkalemia is a pathological condition characterized by an excessively high potassium concentration in plasma, exceeding 5.5 mmol/l. In hyperkalemia, three types can be distinguished depending on the potassium concentration in the blood. This disease most often develops when other factors such as diabetes, kidney failure, or therapy with certain drugs are present. Mild hyperkalemia is often asymptomatic and detected incidentally. Symptoms related to heart function include bradycardia and heart contractions. Treatment of hyperkalemia involves intravenous administration of calcium or glucose with insulin, beta-agonist drugs, hemodialysis, administration of loop diuretics, or forced diuresis. As a modern therapy, treatment with the BPC-157 peptide is used.  

a. BPC-157 Therapy

During hyperkalemia treatment, efforts should be made to remove the cause that led to the increased potassium concentration in the blood, as well as to eliminate the excess potassium in the body. Both of these causes can be eliminated or alleviated through therapy with the peptide BPC-157.

b. Conducted experimental studies

Study 3

Material

The study used male albino rats weighing from 200g to 250g. Study procedure The rats were deeply anesthetized using thiopental and diazepam. To induce severe hyperkalemia, all rats received a high dose of potassium chloride solution intraperitoneally. BPC-157 was administered at a dose of 10 ng/kg ip or 10 μg/kg ip, 30 minutes before the KCl solution. The control group received saline instead of the peptide. 

Results

The effect of BPC-157 at both doses, administered both before and after potassium administration, caused the cessation of the hyperkalemia process. Rats that were not given the peptide died due to excessively high potassium levels in the blood. The effect of the peptide BPC-157 was lasting and sustained, not causing spikes in potassium concentration.

Comparison of the effectiveness of BPC-157 therapy with other substances and a control group in the case of hyperkalemia.

Conclusions

The study demonstrated the full ability of the peptide BPC-157 to combat excessively high potassium levels in plasma. The peptide's effect, both when administered orally and intraperitoneally, is the same, thus showing a wide range of action. Moreover, the peptide BPC-157 is used in cases of fatal, acute hyperkalemia.  

Cardioprotective effect of BPC-157 in relation to conducted studies

The concept of cardioprotection Cardioprotection refers to actions aimed at preventing, limiting, or eliminating the harmful effects of various factors on the heart and its functions. So far, drugs with cardioprotective effects have included ACE inhibitors and ARBs, statins, antiplatelet drugs, and beta-blockers. An innovative method, primarily with a preventive effect but not diminishing the elimination of heart function disorders, is therapy with the peptide BPC-157.  

a. BPC-157 Therapy

One of the disorders affecting the proper functioning of our heart is bradycardia, which is defined as a condition where the heart contracts slower than it should, causing its beating to slow down. According to relatively recent studies, epilepsy may be associated with cardiological diseases. Ventricular arrhythmias or conduction disorders have the same symptoms as epilepsy, but this disorder itself initiates rhythmic epilepsy during which bradycardia occurs. The epilepsy effects induced in the study thus allow the beneficial action of the BPC-157 peptide on pathological phenomena such as bradycardia to be revealed. Bradycardia is often seen in professional athletes but also in hypothyroidism or as a side effect of medications taken. Therapy with the BPC-157 peptide not only creates a "barrier" that acts protectively and prophylactically to shield the heart and improve its function but also reduces undesirable processes related to heart dysfunction. 

b. Conducted experimental studies

Study 4 Material The study was conducted on male albino rats weighing between 200g and 300g. Study procedure Seizures accompanied by bradycardia were induced by administering lidocaine at a dose of 80 mg/kg. BPC-157 at a dose of 10 μg/kg or 10 μg/kg was given immediately after lidocaine administration, along with lidocaine, while the control group received saline. The assessment included the time (in minutes) from the onset of convulsions to their end. The study was conducted under temperature conditions ranging from 20–24°C and humidity of 40-70%.

Results

Bradycardia accompanied by seizures allowed for the assessment of the peptide's effect in this disorder. Administration of BPC-157 at a dose of 10 μg/kg or 10 μg/kg after lidocaine administration reduced the bradycardia effect within minutes. Administration of BPC-157 peptide together with lidocaine prevented the occurrence of bradycardia.   Conclusions BPC-157 exhibits protective, shielding, and heart-protecting effects against potential disorders and also during their occurrence. It reduces and alleviates symptoms of bradycardia and other diseases that may adversely affect the heart, which is essential for the proper functioning of the entire cardiovascular system and the body.

Summary

Proper functioning of the circulatory system is essential for the proper functioning of the body as well as life itself. The spectrum of action of the BPC-157 peptide, which relates to protection, prevention, and alleviation of symptoms, allows it to be defined as a precursor in the treatment of diseases of this system. Systematic use of the peptide will allow for the maintenance of proper circulatory system function and, consequently, the maintenance and improvement of quality of life. The above studies also indicate that BPC-157, both in intraperitoneal and oral forms, exhibits the same action profile. The peptide's effect is rapid and sustained. Therefore, the stable salt form of BPC-157 peptide can be safely and effectively used in all disorders related to the cardiovascular system.

Bibliography

1.Ming-Jer.H, Cheng-Hung.L, Ho-Yen.C, Gwo-Jyh.C, Hsiu-Yun.H, Yuling.L, Jong.P, Modulatory effects of BPC 157 on vasomotor tone and the activation of Src-Caveolin-1-endothelial nitric oxide synthase pathway. 2020; 10: 17078; DOI:10.1038/s41598-020-74022-y 2.Lozic.M, Stambolija.V, Krezic.I, Dugandzic.A, Zivanovic-Posilovic.G, Gojkovic.S, Kovacevic.J, Vrdoljak.L, Mirkovic.I, In relation to NO-System, Stable Pentadecapeptide BPC 157 Counteracts Lidocaine-Induced Adverse Effects in Rats and Depolarisation In Vitro. 2020; 2020: 6805354; DOI:10.1155/2020/6805354 3.Knezevic.M, Gojkovic.S, Krezic.I, Zizek.H, Vranes.H, Malekinusic.D,Complex Syndrome of the Complete Occlusion of the End of the Superior Mesenteric Vein, Opposed with the Stable Gastric Pentadecapeptide BPC 157 in Rats. 2021; 9(8): 1029. DOI:: 10.3390/biomedicines9081029 4.Barisic, Ivan; Balenovic, Diana; Klicek, Robert; Radic, Bozo; Nikitovic, Bojana; Drmic, Domagoj; Udovicic, Mario; Strinic, Dean; Bardak, Darija; Berkopic, Lidija; Djuzel, Viktor; Sever, Marko; Cvjetko, Ivan; Romic, Zeljko; Sindic, Aleksandra; Bencic, Martina Lovric; Seiwerth, Sven; Sikiric, Predrag (2013). Mortal hyperkalemia disturbances in rats are NO-system related. The life saving effect of pentadecapeptide BPC 157. Regulatory Peptides, 181(), 50–66. doi:10.1016/j.regpep.2012.12.007