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3D In Vitro Human Atherosclerosis Model For High-throughput Drug Screening

A new 3D, three-layer nanomatrix vascular sheet that possesses multiple features of atherosclerosis has been applied for developing a high-throughput functional assay of drug candidates to treat this disease, University of Alabama at Birmingham researchers report in the journal Biomaterials in a paper titled "Atherosclerotic three-layer nanomatrix vascular sheets for high-throughput therapeutic evaluation."

"Current in vitro atherosclerosis models have significant limitations, including the lack of three-layer vascular architecture and limited atherosclerotic features," said Ho-Wook Jun, Ph.D., a professor in the UAB Department of Biomedical Engineering and the corresponding author. "Moreover, no scalable 3D atherosclerosis model is available for the evaluation of potential therapeutics via high-throughput assays."

Cardiovascular disease—primarily caused by atherosclerosis—is the leading cause of death in the United States. In the development of effective therapies for atherosclerosis, in vitro models are commonly utilized to assess the efficacy and safety of novel therapeutics before proceeding to complex in vivo and clinical studies.

Recently, the United States Food and Drug Agency Modernization Act 2.0 has permitted the use of alternative models other than animals for drug testing before progressing to human trials. This transformative change in regulations serves as a driving force, inspiring the pursuit of advanced in vitro models, such as cell-based assays and organoid- or artificial intelligence-based models that are capable of replacing or reducing animal use in assessing drug efficacy and safety.

The goal is to expedite progression from preclinical research to human clinical trials via a more efficient and cost-effective drug development process.

The novel in vitro 3D, three-layer nanomatrix vascular sheet with critical atherosclerosis multi-features, or VSA, includes endothelial cell dysfunction, monocyte recruitment, presence of macrophages, extracellular matrix remodeling, smooth muscle cell phenotype transition, inflammatory cytokine secretion, foam cells and calcification initiation. The VSA thus provides a human atherosclerosis-mimicking environment for drug evaluation.

The three layers of the robust vascular sheet, or VS, structure are composed of: 1) human aortic endothelial cells, 2) human aortic smooth muscle cells and 3) human aortic adventitial fibroblasts layers. These mimic the layered structure of the native vascular wall, which, from inside out, is composed of the tunica intima, tunica media and tunica adventitia tissues.

The researchers created the critical atherosclerosis multi-features by adding monocytes and various pro-atherosclerotic cytokines, colony-stimulating factors and oxidized low-density lipoprotein to stimulate atherogenesis on the 3D, layered nanomatrix vascular sheet.

Co-first author Jun Chen, Ph.D., and colleagues used this VSA system to create high-throughput functional assays by fabricating multiple VSAs in 48-well plates. The VSAs were subjected to drug treatments and then were comprehensively characterized, with a focus on evaluating foam cells, inflammation and atherosclerosis-associated genes.

High-throughput functional assays were validated using two classic atherosclerosis drugs, rosuvastatin and sirolimus, and were used to evaluate two drug candidates, curcumin and colchicine, and a potential gene therapy candidate, microRNA-146a-loaded liposomes, for treating atherosclerosis. The researchers found that the VSAs replicated a number of results seen by others in in vivo tests of these treatments.

"The high efficiency and scalability of the VSA-evaluated functional assays should facilitate drug discovery and development for atherosclerosis," Chen said.

"Our study focuses on demonstrating the use of VSAs as a cost-effective and efficient way to investigate therapeutic effectiveness," Jun said.

"The VSAs offer a high-throughput methodology and allow for a relatively large number of biological replicates, also making them ideal for mechanistic research. For instance, VSAs can be customized to induce atherosclerosis on single-, double- or three-layer structures, which provides insights into the effect of discrete layers on atherogenesis, particularly the fibroblast layer. Furthermore, the vascular sheets can be scaled up to develop high-throughput assays for drug safety testing, helping determine pharmacological and toxicological parameters for use in animal models."

The Birmingham-based Endomimetics, LLC, has licensed the new 3D, three-layer nanomatrix vascular sheet atherosclerosis model technology through UAB's Bill L. Harbert Institute for Innovation and Entrepreneurship, which manages university intellectual property.

"The atherosclerosis drug market is a large and growing segment of the pharmaceutical industry," said Joseph Garner, Ph.D., CEO of Endomimetics.

"This market is experiencing significant growth due to the rising prevalence of cardiovascular diseases, advancements in pharmaceutical research and the development of innovative atherosclerosis treatments. By 2032, this market is projected to reach $26.9 billion with a 2.8 percent compound annual growth rate from 2023 to 2032. North America currently holds the dominant market share at more than 41 percent."

Brigitta Brott, M.D., a co-author and an interventional cardiologist and professor in the UAB Department of Medicine Division of Cardiovascular Disease, said, "Endomimetics and UAB will collaborate with pharmaceutical companies to evaluate potential candidates for atherosclerosis treatment, utilizing our VSA-based efficacy and safety assays."

"This approach can also be extended to assess other drugs for conditions such as diabetes, obesity and liver-related diseases, where atherosclerosis is prevalent among many patients."

Endomimetics anticipates providing this innovative atherosclerosis model this spring for evaluating various types of potential therapeutics.

"Our atherosclerosis assays will pave the way for therapeutic candidates directly targeting human plaque and the atherosclerotic artery wall, and they will generate extensive predictive data on their responses, which is crucial for defining the therapeutic window of these candidates and providing essential groundwork for future studies," Jun said.

More information: Jun Chen et al, Atherosclerotic three-layer nanomatrix vascular sheets for high-throughput therapeutic evaluation, Biomaterials (2023). DOI: 10.1016/j.Biomaterials.2023.122450

Citation: 3D in vitro human atherosclerosis model for high-throughput drug screening (2024, January 15) retrieved 31 January 2024 from https://medicalxpress.Com/news/2024-01-3d-vitro-human-atherosclerosis-high.Html

This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.


'I'm A Doctor - Here's A Food To Eat Daily To Slash Your Risk Of Heart Disease'

Heart disease: Doctor explains how to reduce risk in 2021

We all know the famous saying, "You are what you eat". While this may seem trivial there is actually a lot of truth to it.

As a result many of us are focused on the foods to avoid. It is common knowledge that foods high in saturated fats for example are bad for our heart.

However, there are also foods that can have the opposite effect. One expert spoke exclusively with Express.Co.Uk about a popular vegetable that could be eaten daily to help boost heart health.

Doctor Deborah Lee, from the Dr Fox Online Pharmacy, recommended adding plenty of garlic to your meals for this very reason.

It is high in antioxidants, which can help improve blood flow, support the growth of new blood vessels and even prevent atherosclerosis - the deposition of fatty plaques in arterial walls, she said.

Heart attack

Heart disease is one of the biggest causes of death in the UK (Image: Getty Images)

Dr Lee explained: "Garlic achieves these cardioprotective effects by improving the cholesterol profile, inhibiting the production of cholesterol in the liver, lowering blood pressure, having anti-clotting effects by suppressing platelet aggregation, increasing fibrinolysis (clot breakdown) and reducing atherosclerosis."

She referenced a 2022 scientific review on the benefits of garlic, published in Critical Reviews in Food Science and Nutrition.

This concluded that garlic can lower blood pressure, body mass index, waist circumference, "bad" cholesterol, total cholesterol, triglycerides and markers of inflammation.

"It can also raise high density lipoprotein ('good' cholesterol) and has been shown to improve other coronary factors such as reduced coronary artery calcification, the coronary artery microcirculation, and lower the amount of epicardial (fat between the heart muscle and the pericardium, the membrane covering the outside of the heart) and periaortic fat (fat around the main artery of the body – the aorta), as well as reducing the thickness of the coronary artery walls," she said.

Chopping Garlic on Wooden Board

Garlic could help protect the heart, a doctor said (Image: Getty) Become an Express Premium member
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  • "Overall, garlic should be considered a preventative and a treatment for cardiovascular disease (CVD) – this means angina, heart attacks, stroke, peripheral vascular disease and heart failure."

    A separate study from 2016 also found that garlic supplements could reduce systolic (upper reading) blood pressure by 7-16 mmHg, and diastolic (lower reading) blood pressure by 5-9 mm Hg.

    Dr Lee continued: "The British Heart Foundation endorses the fact garlic is good for your heart, but they caution not to rely on garlic alone.

    "It's important to consider your diet as a whole and also have a healthy lifestyle, by not smoking, controlling your weight, drinking less alcohol and taking regular physical exercise."

    Chef puts olive oil in frying pan

    Dr Lee recommended eating an overall healthy diet to protect your heart (Image: Getty) What are some signs that your heart isn't as healthy as it should be?

    Heart and circulatory diseases account for around a quarter of all deaths in the UK.

    Therefore, spotting any of the warning signs is vital.

    Dr Lee said: "In the early stages you may have no symptoms, or they can be very mild, such as shortness of breath or mild chest pain when climbing the stairs, or difficulty sleeping when lying down.

    "You may feel generally fatigued, have slightly swollen ankles and notice an irregular pulse from time to time. But too often a heart attack or a stroke happens out of the blue."

    "Don't wait for heart disease to develop. Take the necessary steps to stay healthy and prevent the onset of heart disease."

    She warned of the following symptoms once heart disease is "established":

  • Angina – Pain in the chest often radiating to the left arm and/or the jaw, on exertion, that gets better with rest
  • Indigestion or heartburn – This can worsen due to the proximity of the oesophagus to the diseased heart
  • A heart attack – This often causes crushing central chest pain, associated with being sweaty, feeling or being sick, feeling light-headed and unwell, and sometimes collapse or loss of consciousness
  • Feeling breathless - This may be especially when lying flat due to fluid building up in the lungs is a sign of heart failure. It may be associated with a cough and/or a chest infection
  • Pain in the calf muscle when you walk, which gets better with rest – This is called claudication, and this is caused by peripheral artery disease – atherosclerosis blocking the arteries and reducing the flow of oxygenated blood to the leg and the foot.
  • A stroke – This can cause sudden headache, face drop on one side of the face, an inability to speak or swallow, loss of function or pins and needles down one side of the body. It can occur with total collapse and loss of consciousness.
  • She added: "If you have any reason to be concerned about your heart, see your GP without delay.

    "You should have your blood pressure checked at least once every five years, and a cholesterol check if you are aged 40 or over, or earlier if you have a history of familial hypercholesterolaemia."


    Aortic Aneurysm Market Worth US$ 9.93 Billion In 2032 - Persistence Market Research

    Global Aortic Aneurysm Market grows with rising cardiovascular cases, driven by an aging population. In North America, advanced technology makes Aortic Aneurysm surgeries minimally invasive for improved outcomes

    New York, Jan. 25, 2024 (GLOBE NEWSWIRE) -- Market Size & Overview:

    The aortic aneurysm market demonstrated significant growth, reaching a market value of US$ 3.34 Billion in 2023, and is projected to achieve a substantial market value of US$ 9.93 Billion by 2032, with a Compound Annual Growth Rate (CAGR) of 11% during the forecast period from 2022 to 2032. This substantial growth is primarily fueled by factors such as the escalating prevalence of atherosclerosis and the increasing elderly population.

    The prevalence of atherosclerosis, a condition characterized by the accumulation of plaque in the arteries, is considered a major contributor to the expansion of the aortic aneurysm market. As atherosclerosis is a significant risk factor for aortic aneurysms, the rising incidence of this condition is driving the demand for treatments and interventions related to aortic aneurysms.

    Moreover, the growing geriatric population is another key factor influencing the market's growth. With an aging population, the incidence of aortic aneurysms tends to rise, as age is a known risk factor for the development of this condition. The aging demographic, therefore, contributes to the overall expansion of the aortic aneurysm market.

    The market is also benefiting from the increasing preference for minimally invasive procedures. Minimally invasive techniques offer advantages such as reduced recovery time, lower risk of complications, and shorter hospital stays, making them increasingly popular among both patients and healthcare providers.

    Additionally, favorable health reimbursement policies are playing a crucial role in boosting market growth. The availability of reimbursement for aortic aneurysm-related procedures and treatments encourages patients to seek timely medical intervention and contributes to the overall market expansion.

    Story continues

    Request for SAMPLE copy of report: https://www.Persistencemarketresearch.Com/samples/33177

    Market Scope:

    Report Coverage

    Details

    Market Revenue 2023

    US$ 3.34 Billion

    Estimated Revenue 2030

    US$ 9.93 Billion

    Growth Rate - CAGR

    11%

    Forecast Period

    2023-2030

    No. Of Pages

    296 Pages

    Market Segmentation

  • Type

  • Treatment

  • Product

  • End-User

  • Region

  • Regions Covered

  • North America

  • Europe

  • Latin America

  • East Asia

  • The Middle East & Africa

  • South Asia & Pacific

  • Key Companies Profiled

    In a nutshell, the Persistence Market Research report is a must-read for start-ups, industry players, investors, researchers, consultants, business strategists, and all those who are looking to understand this industry. Get a glance at the report at: https://www.Persistencemarketresearch.Com/market-research/aortic-aneurysm-market.Asp

    Market Growth Drivers:

    Increasing Prevalence of Atherosclerosis: The rising incidence of atherosclerosis, a condition characterized by the buildup of plaque in the arteries, is a significant driver for the aortic aneurysm market. Atherosclerosis is a major risk factor for the development of aortic aneurysms, and as its prevalence grows, so does the demand for treatments related to aortic aneurysms.

    Aging Global Population: The demographic shift towards an aging population is a major driver for the market. Aortic aneurysms are more common in older individuals, and as the global population ages, the incidence of aortic aneurysms is expected to rise, contributing to the overall growth of the market.

    Rising Geriatric Population: The aging demographic is specifically highlighted as a growth driver. Older individuals are more susceptible to aortic aneurysms, and the increasing number of elderly people globally is fueling the demand for interventions and treatments related to this condition.

    Increasing Demand for Minimally Invasive Procedures: The market is benefiting from the growing preference for minimally invasive procedures. Minimally invasive techniques offer advantages such as quicker recovery, reduced risk of complications, and shorter hospital stays, making them increasingly popular among both patients and healthcare providers.

    Favorable Health Reimbursement Policies: The presence of favorable health reimbursement policies is playing a crucial role in market growth. Access to reimbursement for aortic aneurysm-related procedures and treatments encourages patients to seek timely medical intervention, thereby contributing to the overall expansion of the market.

    Market Restraints:

    High Treatment Costs: The cost associated with the treatment of aortic aneurysms, especially advanced and surgical interventions, can be high. This may pose a challenge for patients, healthcare providers, and healthcare systems, potentially limiting the accessibility of certain treatments and affecting overall market growth.

    Limited Awareness and Diagnosis: Lack of awareness about aortic aneurysms and their symptoms may result in delayed diagnosis and treatment. Limited awareness among both patients and healthcare professionals could hinder early intervention, impacting the overall market growth.

    Stringent Regulatory Approval Processes: The medical devices and procedures used in the treatment of aortic aneurysms are subject to regulatory approval processes. Stringent regulatory requirements can extend the time and resources needed for product development and market entry, potentially slowing down the introduction of new technologies and treatments.

    Complications and Risks Associated with Procedures: Despite advancements in medical technology, interventions for aortic aneurysms, whether surgical or minimally invasive, can carry risks and potential complications. Concerns about these risks may influence patient and physician decision-making, impacting the adoption rate of certain procedures and treatments.

    Limited Healthcare Infrastructure in Developing Regions: In some developing regions, there may be limitations in healthcare infrastructure, including access to specialized medical facilities and trained healthcare professionals. This could affect the timely diagnosis and management of aortic aneurysms, acting as a restraint to market growth in these areas.

    Opportunities:

    Technological Advancements: Ongoing advancements in medical technologies, including imaging, surgical techniques, and device innovations, present opportunities for the development of more effective and less invasive treatments for aortic aneurysms. Novel technologies can enhance diagnostic accuracy and improve patient outcomes.

    Patient Education and Awareness Programs: Opportunities exist to invest in educational initiatives aimed at raising awareness about aortic aneurysms, their risk factors, and symptoms. Increased awareness can lead to earlier diagnosis and intervention, potentially reducing the severity of cases and improving overall patient outcomes.

    Global Expansion in Emerging Markets: There is potential for market expansion in emerging economies where healthcare infrastructure is improving. Increased access to healthcare services and growing awareness about cardiovascular health in these regions create opportunities for the aortic aneurysm market to expand its reach.

    Collaboration and Partnerships: Collaborative efforts between healthcare providers, research institutions, and industry players can accelerate research and development initiatives. Partnerships can lead to the creation of innovative solutions, new treatment modalities, and improved patient care pathways.

    Remote Patient Monitoring and Telemedicine: The integration of remote patient monitoring and telemedicine in the management of aortic aneurysms can enhance healthcare delivery. Remote monitoring solutions can enable timely intervention, reduce hospital visits, and improve patient adherence to treatment plans.

    Regional Insights

    Technological Advancements Making Surgeries Minimally Invasive for Aortic Aneurysm in North America?

    Rapid technological advancements, a shift to minimally invasive procedures, and increased incidence of Abdominal Aortic Aneurysms (AAAs) drive market growth. The U.S. SAVE Act, offering free AAA screenings, and high reimbursements, especially through Medicare, contribute to the market's expansion. North America is poised to hold a significant 47% market share in 2022, highlighting a favorable environment for aortic aneurysm market development.

    High Prevalence of atherosclerosis Driving Growth of Aortic Aneurysm Market in Europe?

    Europe is expected to be a significant player in the aortic aneurysm market, holding a 30% market share in 2022. This is attributed to technological advancements and the proactive efforts of organizations like the National Health Service (NHS) in implementing screening programs to identify individuals at risk, allowing for early treatment and informed decision-making.

    Category-Wise Insights

    Increasing Occurrence of Diseases in the Geriatric Population Making AAA the Dominant Category?

    Abdominal Aortic Aneurysm (AAA) is more prevalent in the lower abdomen, comprising over 70% of the market in 2022. With higher repair rates than Thoracic Aortic Aneurysms (TAA), AAA is a focus of robust research and development, supported by government approvals. Circulation reports a 2.5% prevalence in adults over 65 for AAA, whereas TAA is less common at 4.5% to 5.9% per 100,000 person-years.

    Technological Advancements to Reduce Hospital Stays Increasing Dependency on EVAR Treatments?

    The aortic aneurysm market is divided into open surgical repair (OSR) and endovascular aneurysm repair (EVAR). The increasing global acceptance of endovascular treatment, coupled with technological advancements reducing hospital stays, is driving growth in the EVAR segment. In the U.S., 75% of procedures in 2017 were EAVR, and with anticipated new product launches, the EVAR segment is expected to capture a 70% market share in 2022.

    Some of the market players:

  • Medtronic: Medtronic is a global medical technology company that specializes in the development and manufacturing of medical devices and therapies. It is known for its contributions to various healthcare fields, including cardiovascular solutions.

  • Endologix LLC: Endologix is a medical technology company focused on the treatment of aortic disorders, particularly abdominal aortic aneurysms. The company develops innovative endovascular technologies to provide minimally invasive treatment options.

  • Gore Medical: Gore Medical, a division of W. L. Gore & Associates, is recognized for its expertise in materials science and its applications in medical devices. The company is involved in the development of vascular grafts and other medical products.

  • MicroPort Scientific Corporation: MicroPort Scientific Corporation is a multinational medical device company with a focus on the development and manufacturing of high-quality medical solutions. The company operates in various therapeutic areas, including cardiovascular devices.

  • Cook: Cook Medical is a family-owned medical device company known for its contributions to the healthcare industry. Cook develops a wide range of medical devices, including those used in cardiovascular interventions and aortic aneurysm treatment.

  • JOTEC: JOTEC is a company specializing in the development of medical devices for cardiovascular and peripheral vascular applications. Their product portfolio includes solutions for aortic and vascular surgery.

  • Cardinal Health: Cardinal Health is a global healthcare services and products company that operates in various segments of the healthcare industry. It is involved in the manufacturing and distribution of medical products, including those related to cardiovascular health.

  • Terumo Corporation: Terumo Corporation is a Japanese medical device company with a global presence. It is engaged in the development and manufacturing of a wide range of medical products, including devices for cardiovascular interventions.

  • Lombard Medical: Lombard Medical, now part of MicroPort Scientific Corporation, was known for its focus on the development of endovascular solutions for the treatment of abdominal aortic aneurysms.

  • AbbVie Inc.: AbbVie is a multinational pharmaceutical company with a diverse portfolio of healthcare products. While not exclusively focused on aortic aneurysm solutions, AbbVie may be involved in related pharmaceuticals or supportive therapies.

  • Key Segments Profiled in the Aortic Aneurysm Industry Survey

    Aortic Aneurysm by Type

    Aortic Aneurysm by Thoracic Aortic Aneurysm (TAA)

    Aortic Aneurysm by Abdominal Aortic Aneurysm (AAA)

    Aortic Aneurysm Treatment

    Aortic Aneurysm by Open Surgical Repair (OSR)

    Aortic Aneurysm by Endovascular Aneurysm Repair (EVAR)

    Aortic Aneurysm Product

    Aortic Aneurysm by Stent Grafts

    Aortic Aneurysm by Catheters

    Aortic Aneurysm End User

    Aortic Aneurysm by Hospitals

    Aortic Aneurysm by Ambulatory Surgery Centers

    Aortic Aneurysm by Clinics

    Aortic Aneurysm Region

    North America Aortic Aneurysm Market

    Latin America Aortic Aneurysm Market

    Europe Aortic Aneurysm Market

    Asia Pacific Aortic Aneurysm Market

    Middle East & Africa Aortic Aneurysm Market

    About Persistence Market Research:

    Business intelligence is the foundation of every business model employed by Persistence Market Research. Multi-dimensional sources are being put to work, which include big data, customer experience analytics, and real-time data collection. Thus, working on "micros" by Persistence Market Research helps companies overcome their "macro" business challenges.

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