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Take a closer look at how peptide therapy supports heart health and cardiovascular function, exploring the mechanisms, clinical evidence, and types of peptides involved.
Peptide therapy is gaining a lot of attention in the medical field. Between 2016 and 2022, the FDA approved 26 peptide-based drugs. Today, more than 200 peptides are being tested in clinical trials, and around 600 are still in early research stages.
One area where peptide therapy shows promising potential is in treating cardiovascular diseases (CVDs). It’s the world’s leading cause of death, claiming around 17.9 million lives each year. With CVD-related deaths rising by about 40% between 1990 and 2013 due to population growth and aging, there’s an urgent need for more effective treatment options.
This article takes a closer look at how peptide therapy supports heart health and cardiovascular function, exploring the mechanisms, clinical evidence, and types of peptides involved.
Peptides are short chains of amino acids, typically made up of 2 to 50 amino acids linked together by peptide bonds. Amino acids are the building blocks of proteins, and when they connect in specific sequences, they form peptides.
The number of amino acids in a chain helps name the peptide:
If the chain gets longer than 50 amino acids, it’s usually considered a protein.
Peptides naturally occur in the body and are involved in many important biological functions, such as:
Examples of naturally occurring peptides include insulin, oxytocin, and glucagon.
Peptide therapy involves using natural or synthetic peptides as medical treatments.
Therapeutic peptides come from many sources. Some are found in nature, produced by plants, animals, or even the human body, like peptide hormones. Others use synthetic chemical libraries, genetic engineering, and recombinant technologies. Scientists can also design new peptides using computer-based (bioinformatic) methods.
Unlike small-molecule drugs such as losartan or metformin, peptide-based drugs are usually more selective. They target specific cells or receptors and often work at very low doses. This focused action may lower the chance of side effects because they don’t affect other body parts as much.
Peptides are also broken down in the body in ways that are easier to predict. Plus, their breakdown products are generally safe. They also don’t often interfere with liver enzymes like CYP450, which means they are less likely to interact with other medications.
Peptide-based therapies aren’t new. One of the earliest examples is insulin, a peptide hormone used to manage diabetes since the 1920s.
Another example is nesiritide, sold under the brand name Natrecor. It was approved by the US FDA in 2001 for treating acute decompensated heart failure (ADHF). However, it was later discontinued in 2018 by its manufacturer, Janssen Pharmaceuticals.
GLP-1 medications like Ozempic, Victoza, and Wegovy are FDA-approved to lower the risk of serious heart problems, such as heart attack or stroke, in adults with type 2 diabetes who already have heart disease.
Some of the most commonly used drugs for type 2 diabetes and weight loss, like Ozempic, Wegovy, and Saxenda, are actually based on peptides. More specifically, they’re GLP-1 receptor agonists, designed to act like the body’s natural GLP-1 hormone (glucagon-like peptide-1).
While primarily used to manage blood sugar and support weight loss, recent studies suggest they may also offer benefits for atherosclerosis.
In one study, researchers showed that even without affecting blood sugar, GLP-1 receptor activity appears to protect the heart. It may help shift macrophages to the M2 (healing) type, potentially slowing down plaque progression in coronary artery disease. This points to a direct anti-inflammatory and cardiovascular benefit of GLP-1 beyond diabetes control.
Another study suggests that GLP-1 protects the endothelium from damage caused by high blood sugar. This effect is especially relevant for people with type 2 diabetes, who face a higher risk of cardiovascular disease.
Other peptide-based strategies are also being explored. Scientists are developing peptide-loaded nanoparticles designed to target specific cells involved in atherosclerosis, such as:
Some peptides are engineered to bind to collagen and help strengthen the fibrous cap of arterial plaques, which may reduce the risk of rupture. In addition, researchers are using computer simulations to study peptides derived from sea urchin spines that may target proteins linked to the progression of atherosclerosis.
In conditions like ischemic heart disease, where blood supply to the heart is limited, encouraging new blood vessel formation (known as angiogenesis) is critical. Restoring circulation can improve the heart’s pumping ability and ease symptoms like chest pain.
Among the earliest peptides studied for this purpose is Thymosin beta-4 (Tβ4), a naturally occurring peptide with strong regenerative potential. Research has long explored its role in wound healing, tissue repair, and blood vessel formation.
In a 2014 study involving mice that had experienced heart attacks, those treated with Tβ4 showed significantly better outcomes:
More recently, researchers identified peptide Lv, also a naturally occurring peptide. Peptide Lv activates VEGFR-2, a receptor essential for blood vessel formation, vasodilation (widening of blood vessels), and processes related to both normal development and disease.
In both lab settings and animal models, peptide Lv encouraged blood vessel cells to grow and form new networks.
High blood pressure (hypertension) is one of the main risk factors for developing heart disease. It’s often caused by:
Scientists are exploring many types of peptides to treat high blood pressure and heart disease. These therapies target different systems in the body, including:
A natural system that helps regulate blood pressure involves natriuretic peptides. They help by relaxing blood vessels and removing extra salt and water from the body. These include:
MANP is a lab-designed version of ANP. Scientists made MANP by adding 12 extra amino acids to the original ANP hormone. This change makes it last longer in the body and resists enzyme breakdown.
Compared to natural ANP, MANP produces stronger effects:
Researchers also believe MANP may help prevent heart enlargement, tissue scarring, and cell overgrowth, which are common in long-term high blood pressure.
In 2024, researchers conducted the first-in-human study involving 22 participants with high blood pressure and metabolic syndrome (MetS) to see if subcutaneous injection of MANP was safe, tolerable, and effective. The blood pressure effects were modest, but the metabolic benefits were stronger.
Researchers are also exploring peptides found in food and natural sources to treat high blood pressure by acting on the renin-angiotensin system (RAS). Within the RAS:
Because of this, targeting RAAS is a common strategy to treat high blood pressure and heart problems.
Many of these peptides come from dairy, eggs, and meat. IPP (Isoleucine-Proline-Proline) and VPP (Valine-Proline-Proline) are two of the most well-studied peptides. They work by inhibiting ACE, the same target used by ACE inhibitor drugs like lisinopril.
In one study, people who took these peptides had a drop of 4.8 mmHg in systolic blood pressure and 2.2 mmHg in diastolic blood pressure.
Plants are also good sources of blood pressure-lowering peptides. A soy-derived four-amino acid peptide called FGSF (Phe-Gly-Ser-Phe) lowered blood pressure in hypertensive rats by nearly 22 mmHg.
Even yeast and algae can produce antihypertensive peptides. Spirulina, a type of blue-green algae, contains peptides (IQP and VEP) that help lower blood pressure by balancing the RAS system. They reduced harmful components like ACE and angiotensin II, while increasing helpful components like ACE2 and angiotensin 1-7.
In a 2021 meta-analysis, food-derived peptides lowered systolic BP by 3.28 mmHg and diastolic BP by 1.82 mmHg.
Your body naturally produces reactive oxygen species (ROS) during normal metabolism. This happens in all organisms that use oxygen. Usually, your body keeps ROS levels in balance by removing the excess. But when you're under stress, either from inside (like high blood sugar) or outside (like UV light), ROS levels can spike. This leads to oxidative stress, which damages important molecules in your body like DNA, proteins, and fats.
Too much ROS isn’t just harmful, it’s linked to many diseases, including damage to cardiac cells, and contributes to heart failure.
Some peptides possess antioxidant properties or promote the activity of antioxidant enzymes, offering protection against oxidative damage.
In a 2023 study, researchers looked at three short peptides, KA-8, LR-7, and PG-7, that were extracted from the protein of a fish called Harpadon nehereus. These peptides were tested on liver cells that were exposed to high glucose levels, to mimic damage similar to what happens in diabetes.
All three peptides helped improve cell health and lower harmful markers. But LR-7 was best at improving both antioxidant defenses and glucose metabolism. It helped liver cells produce more protective and metabolic proteins, which help defend against oxidative stress and improve glucose metabolism.
Another study examined bioactive peptides in red millet yellow wine. When tested on heart cells exposed to oxidative stress, the peptides helped protect the cells and improved their survival.
High levels of “bad” cholesterol (LDL) are one of the main reasons people develop heart disease. In contrast, HDL, known as “good” cholesterol, helps clear excess cholesterol from the blood by carrying it to the liver for removal.
A key protein in this process is Apolipoprotein A-I (ApoA-I). It works with a gene called ABCA1 to pull cholesterol out of cells, especially foam cells, which are the type that build up in artery walls and contribute to heart disease.
Researchers developed a synthetic peptide called FAMP (Fukuoka University ApoA-I Mimetic Peptide) to imitate ApoA-I's cholesterol-clearing ability. While ApoA-I is made up of 243 amino acids, FAMP is much smaller, with only 24. It was specifically designed to work with ABCA1, making it more targeted and potentially more effective.
In animal studies, 16 weeks of FAMP treatment reduced plaque buildup by about 50% in mice fed a high-fat diet.
In 2016, researchers showed that FAMP also promoted blood vessel growth and restored blood flow in mice that had poor circulation in one leg due to a high-cholesterol diet.
Peptides have a lot of medical potential, but they also come with several challenges, especially regarding how they behave in the body. Scientists summarize a drug’s journey through the body using the acronym ADME, which stands for Absorption, Distribution, Metabolism, and Excretion. These factors determine how well a drug works in the body and where it goes.
If you take a peptide drug by mouth, your body has to absorb it through your gut and into the bloodstream. That’s where things get tricky.
Peptides don’t pass easily through the lining of your digestive tract. Most drugs need to be small, slightly fatty (lipophilic), and not too polar to pass through cell membranes. But peptides are usually the opposite–too big, too water-loving, and they don’t pass through membranes easily.
Even if a peptide could get through the gut wall, it has to survive the harsh environment of the digestive system. Peptides can:
Some scientists have figured out ways to make peptides more stable in the gut, but the real challenge is still getting them through the gut wall into your bloodstream.
That’s why most peptide-based drugs have to be injected, not swallowed.
Because peptides can’t easily cross cell membranes, they mostly stay in the bloodstream and don’t reach targets inside cells. Also, they can’t cross the blood-brain barrier (BBB) unless there’s a special transport system.
Peptides don’t stay in the body for long. They’re either:
Even if a peptide is stable enough to avoid enzymes, it usually disappears from the blood within minutes. That’s a problem for treating long-term (chronic) conditions. However, it can be useful in emergencies when a fast-acting, short-lived drug is ideal.
On top of the biological issues, making peptides is about 10 times more expensive than making small-molecule drugs. This is because it involves many steps and complicated purification.
That said, newer methods like catch-and-release purification are helping reduce those costs. This technique helps isolate only the correct peptide, making the whole process more efficient and less wasteful.
In cardiovascular health, peptides can improve blood vessel function, lower blood pressure, reduce inflammation, and promote healing after heart damage. While the science is still developing, early results are promising.
If you're managing a heart condition or looking to prevent one, discussing peptide therapy with a qualified provider may be worthwhile. GLP-1 drugs like Ozempic and Victoza, originally for diabetes, have also been shown to protect the heart.
