Millions of lives are claimed by cardiovascular diseases annually, also causing economic burdens all over the world. Although treatments are advanced and prevalent, there are doubts about the potential risks and side effects of surgeries and treatments.
To tackle this problem, we utilized two peptides to alleviate the effects of:
as a prevention method for CVDs.
Our iGEM project aims to produce a fusion protein, TP1-P5, which is created by combining ginsentide TP1, extracted from ginseng, and lupin peptide P5, extracted from lupin plants. Our development of the fused protein TP1-P5 will fill the gaps in providing a more affordable, effective, and comprehensive cardiovascular preventive supplement for high-risk elderly populations.
Cardiovascular diseases (CVDs) are the leading cause of mortality globally, responsible for a significant number of deaths. In recent years, 20.5 million lives have been claimed by CVDs. Statistics also show that around 620 million people are suffering from symptoms of heart and circulatory diseases across the world. Globally, it’s estimated that 1 in 13 people have been diagnosed with heart or circulatory diseases. href="https://www.bhf.org.uk/-/media/files/for-professionals/research/heart-statistics/bhf-cvd-statistics-global-factsheet.pdf?rev=e61c05db17e9439a8c2e4720f6ca0a19&hash=6350DE1B2A19D939431D876311077C7B#:~:text=Globally%20it's%20estimated%20that%201,a%20heart%20or%20circulatory%20disease.&text=and%20260%20million%20men">[Data Source]
Atherosclerosis is a coronary disease and a major source of morbidity in developed countries. A chronic, progressive condition, it is the primary cause of most CVDs. Through research, we discovered that the prevalence of atherosclerosis varied between 17% in individuals younger than 20 years old, to 85% in subjects above 50 years old. Atherosclerosis significantly increases the risk of serious cardiac injury, subsequently triggering the formation of thrombus and hence thrombosis. Thrombosis is the most common underlying pathology of the three major cardiovascular disorders: ischemic heart disease (acute coronary syndrome), stroke, and venous thromboembolism (VTE).
[Atherosclerosis Study] [Stroke Prevention] [VTE Information]
Statistics demonstrated that atherosclerosis resulted in $100 billion in annual costs in the United States alone. CVDs are amongst the most costly chronic conditions to treat. In the United States, the estimated direct healthcare costs associated with CVDs, including medications, hospital stays, etc., were 363.8 billion USD in 2024, as stated by the American Heart Association. The cost is expected to continue rising due to the development of expensive treatments, an ageing population, etc. In a nutshell, cardiovascular disease is a serious problem that has to be solved, regardless of population health or economics.
Currently, there are several main types of treatment for cardiovascular diseases: pharmacotherapy, coronary angioplasty, and polypill.
[Pharmacotherapy Overview] [Angioplasty Information]
Pharmacotherapy is the treatment of health conditions by using pharmaceutical products (drugs) as medication. For cardiovascular diseases, antiplatelet agents (e.g., Aspirin, Clopidogrel) are used to prevent blood clots. Side effects may include gastrointestinal bleeding and increased risk of hemorrhage. Statins (e.g., Simvastatin) lower cholesterol levels and reduce the risk of heart attacks. Side effects may include muscle pain, liver damage, and increased blood sugar levels. Loop diuretics (e.g., furosemide) are used in management and treatment in fluid overflow conditions. Side effects, especially in elders with chronic heart failure, include dizziness, headache, gastrointestinal upset, hyponatremia, hypokalemia, and dehydration.
[Dizziness Information] [Dehydration Info]
Apart from the side effects of the drugs themselves, affordability is the major barrier for low-income countries. In middle- and low-income countries, aspirin and β-blockers were widely available and affordable, but ACE-I/ARBs and statins were less widely available and relatively unaffordable.
Coronary angioplasty is a procedure that uses a balloon or stent to open narrowed or blocked arteries, improving blood flow to the heart. While effective, it carries risks such as:
https://static.igem.wiki/teams/5063/description-2-0/pcardio20140402v0001.jpg These risks can escalate significantly based on clinical factors, such as:
For more details, visit the Johns Hopkins Medicine page or MyHealth Alberta.
The polypill combines various medications, including:
It aims to enhance medication adherence and reduce the risk of CVD. However, it may also increase the risk of side effects, particularly in sensitive individuals.
Despite the availability of effective treatments, the current approach to CVD management presents several issues:
PMC StudyTo address these challenges, an innovative, affordable, and safe alternative for CVD treatment is being developed, focusing on traditional Chinese medicine. Research has indicated that certain Chinese medicinal herbs may possess CVD-treating properties, which will be complemented by plant-based peptides.
The cardiovascular health supplements market is projected to grow significantly, indicating a rising demand for effective CVD management solutions.
Ginseng is a medicinal plant that has been used for centuries in traditional medicine systems, particularly in Asia. It is available in different species, with Asian ginseng (Panax ginseng) and American ginseng (Panax quinquefolius) being the most commonly used. Ginseng is known for its adaptogenic properties, believed to help the body cope with stress and promote overall well-being.
Ginsentides are different from ginsenosides; they share similarity in certain bioactive functions but differ in magnitude. Ginsentides are disulphide-rich, cell-penetrating, and proteolytic-stable microproteins. It reduces phenylephrine-induced vasoconstriction. The cell-penetrating superdisulfide peptides or microproteins such as ginsentides would have advantages over unconstrained peptides. Ginsentide and ginsentide-like peptides would also have an advantage over small-molecule metabolites whose footprints are too small to inhibit intracellular protein interactions.
Ginsentides are not to be confused with ginsenosides which share similarity in certain bioactive functions but differ in magnitude. Ginsentide TP1 (hereafter given as TP1), derived from ginseng, a medicinal plant that has been used for centuries in traditional medicine systems, particularly in Asia. It is available in different species, with Asian ginseng (Panax ginseng) and American ginseng (Panax quinquefolius) being the most commonly used. Ginseng is known for its adaptogenic properties, believed to help the body cope with stress and promote overall well-being.
We later discovered another plant-based peptide, lupin peptide P5, derived from lupin beans, which has similar CVD treating properties as ginseng; it specializes in targeting preliminary stages of CVDs, complementing the effectiveness of the original supplement. Lupin beans are yellow legume seeds from lupinus albus, a plant mostly found in Mediterranean countries. They are considered a super bean because of all the health benefits packed inside the small bean. The lupin bean exceeds most other beans in its fiber content, making them perfect for preventing many heart-related diseases.
Lupin peptide P5, derived from lupin beans, represents a novel approach to cholesterol regulation, functioning through competitive inhibition of HMG-CoA reductase and counteracting PCSK9-mediated LDL receptor degradation. By lowering cholesterol production and enhancing LDL clearance, it offers a promising strategy for cardiovascular disease prevention.
Our iGEM project is centered on producing a fusion protein, TP1-P5. By combining ginsentide TP1 with lupin peptide P5, we aim to develop a more effective and affordable cardiovascular supplement. This fusion protein addresses significant gaps in the current market, where many existing products lack comprehensive benefits or are prohibitively expensive.
Our strategy involves the cost-effective biosynthesis of TP1-P5 in E. coli, ensuring accessibility for a broader audience. We believe that this innovative supplement can play a vital role in promoting cardiovascular health, ultimately contributing to better health outcomes for individuals at risk of heart disease. Through our project, we hope to pave the way for advancements in functional foods and nutraceuticals.
Last but not least, also these: