Atherosclerosis Research & Treatment Through the Years: Where we’ve been and where we’re going
Atherosclerosis Treatment Through the Years
Atherosclerosis is a complex and multifactorial disease characterized by the buildup of plaques within the arteries, leading to the narrowing and hardening of these blood vessels. This narrowing and hardening of blood vessels can lead to reduced blood flow and increase your risk of cardiovascular events Over the years, treatment strategies for atherosclerosis have evolved, but there is still a need for more effective therapies to combat this prevalent disease. In this blog post, we will explore the past, present, and future of atherosclerosis treatment, highlighting the challenges and advancements in this field.
History of Atherosclerosis Treatments
The earliest known treatments for atherosclerosis were not well documented, but some historical figures have described the disease and its symptoms.
Leonardo Da Vinci was among the first to describe atherosclerosis, stating that “vessels in the elderly restrict the transit of blood through thickening of the tunics.”1 He did not suggest any treatment, however, as this disease was not yet well understood.
The first detailed and accurate description of “arteriosclerosis” is contributed to Italian surgeon and academic, Antonio Scarpa, who lived from 1752-1832. He described a “slow degeneration…of the internal coat of the artery.” The word “atherosclerosis”, however, was introduced in 1904 by German pathologist Felix Marchand who emphasized the presence of lipid material causing vascular stiffening and obstructions2.
In the past, the primary focus of atherosclerosis treatment was on risk factor modification and medical therapy. Since cholesterol is predominant in plaque, treatment focused on the reduction of cholesterol and surgical or mechanical repair of the restrictions caused by plaque buildup. However, these treatments were not curative and merely delayed the progression of the disease.
Present Atherosclerosis Treatments
At present, the treatment approach for atherosclerosis has expanded to include various modalities. Lifestyle modifications, such as smoking cessation, regular exercise, and healthy diet choices, play a vital role in reducing risk factors. Pharmacological interventions, such as lipid-lowering drugs, anti-inflammatory agents, and blood pressure-lowering medications, are commonly prescribed. While these treatments have shown some efficacy, they often fall short of effectively reducing the risk of atherosclerosis development4.
While there are established risk factors for atherosclerosis, such as high cholesterol, smoking, hypertension, and diabetes, it is apparent from failures in current prevention and treatment models that there are other factors contributing to the progression of this disease.
Ongoing Atherosclerosis Clinical Research
Ongoing research into the future of atherosclerosis treatment is continuously uncovering new insights into the underlying causes of this condition. Several areas of investigation have gained prominence in recent years researching the impact of these factors on the development and progression of atherosclerosis:
1. Inflammation and Immune Response
Research has shown that inflammation plays an important role in the development of atherosclerosis. Chronic inflammation triggers an immune response, which attracts immune cells to the arterial walls. These cells engulf lipids, turning into foam cells. These foam cells accumulate within the arterial plagues. Scientists are investigating various inflammatory pathways and immune cell interactions to understand the intricate mechanisms that contribute to atherosclerosis.
2. Genetic Factors
Studies have consistently shown a link between genetics and the risk of developing atherosclerosis. Researchers are identifying specific genes and genetic variations associated with increased risk, such as those involved in lipid metabolism, inflammation regulation, and oxidative stress. Understanding the genetic underpinnings of atherosclerosis could lead to personalized and targeted risk assessments and interventions in the future.
3. Epigenetics
Epigenetic modifications are heritable changes in gene expression that do not involve altering DNA sequences. Researchers are exploring how epigenetic modifications, such as DNA methylation, histone modifications, and microRNAs, influence atherosclerosis development. This research aims to uncover the epigenetic changes that occur in response to atherosclerosis risk factors. This can also help reveal the impact of risk factors on gene regulation related to atherosclerosis.
4. Gut Microbiota
Emerging evidence suggests a potential link between gut microbiota, or the microorganisms in your GI tract, and atherosclerosis. The composition of the microbial community in your gut can affect lipid metabolism, inflammation, and immune responses, all of which play crucial roles in the progression of atherosclerosis. Ongoing research aims to clarify the interactions between gut microbiota, host metabolism, and the development of atherosclerotic plaques.
5. Environmental Exposures
Researchers are investigating the impact of various environmental factors on atherosclerosis. For example, air pollution has been associated with increased cardiovascular risk, including the development of atherosclerosis. Other exposures under scrutiny include heavy metals, chemicals, and endocrine disruptors (found in plastics, pesticides, and other agents). Understanding how these environmental factors contribute to atherosclerosis can guide preventive care and public health initiatives.
6. Cellular Senescence
Cellular senescence refers to the irreversible arrest of cells that typically occurs as a response to stress or damage. When cells arrest, the cell stops functioning adequately due to impaired intercellular communication and compromised tissue function that leads to inflammation. This process eventually induces cell death, but can also lead to accumulation of senescent cells in arterial walls. This accumulation is linked to atherosclerosis development. Current research focuses on understanding the mechanisms by which senescent cells contribute to plaque formation and identifying therapeutic approaches to remove or rejuvenate these cells
The development of new therapies is essential to address the underlying causes of atherosclerosis. Researchers are investigating novel drugs and therapeutic approaches that go beyond traditional lipid-lowering strategies and address the potential contributing factors above. By targeting different mechanisms involved in the disease process, these new therapies aim to provide more comprehensive and effective treatment options.
Lipoprotein (A) and Atherosclerosis
One factor that is being closely looked at is Lipoprotein (a), or “Lp(a)”. Lp(a) is a unique lipoprotein particle made up of a low-density lipoprotein (LDL) bound to a glycoprotein called apolipoprotein(a), or “apo(a)”. Elevated Lp(a) levels contribute to atherosclerotic heart disease through mechanisms involving arterial wall deposition, inflammation, and thrombosis.
High levels of Lp(a) in the blood have been identified as an independent risk factor for the development and progression of atherosclerotic heart disease (ASHD) and other cardiac illnesses such as coronary artery disease, myocardial infarction, and stroke, even in individuals with well-controlled LDL cholesterol levels. The measurement of Lp(a) may have value in identifying individuals at higher risk for atherosclerosis.
Lipoprotein (a)’s impact on Atherosclerotic Heart Disease
Lp(a) is believed to contribute to ASHD through multiple mechanisms:
- Lp(a) is strongly attracted to artery walls, and when levels rise in the bloodstream, it gets deposited on vessel walls, triggering the start of atherosclerotic plaque formation.
- Lp(a) possesses pro-inflammatory and pro-thrombotic properties, promoting inflammation and blood clotting within the arteries. This further exacerbates plaque formation and destabilization.
The Genetic Link to Atherosclerosis
The size and concentration of Lp(a) in the bloodstream can vary widely among individuals due to genetic factors. Genetic studies have revealed that Lp(a) levels are predominantly determined by a gene called LPA, which encodes apo(a). Variations in this gene influence the size of the apo(a) protein and, consequently, Lp(a) levels. Certain genetic variants are associated with higher Lp(a) levels and an increased risk of atherosclerotic heart disease. This emphasizes the importance of family history in the development and progression of atherosclerosis.
Future Research in Lipoprotein (a)
Given the link between Lp(a) and atherosclerosis, there is a growing interest in incorporating testing Lp(a) levels in the blood within clinical practice. This may help in refining risk assessments and screens, particularly in individuals with a strong family history of atherosclerosis or who have unexplained, premature cardiovascular events. However, determining the exact Lp(a) levels for intervention and specific treatments is an ongoing process.
Ongoing research aims to develop targeted therapies that lower Lp(a) concentrations, as lifestyle modifications and currently available lipid-lowering therapies have limited impact on reducing Lp(a) concentrations. Novel agents, such as antisense oligonucleotides and monoclonal antibodies targeting apo(a), are being developed to specifically lower Lp(a) levels and evaluate their efficacy in reducing risk of developing atherosclerosis.
The Future of Atherosclerosis Treatment
Atherosclerosis treatment has come a long way, from risk factor modification and medical therapy in the past to a more comprehensive approach in the present. However, the limitations of current therapies and the persistent burden of atherosclerosis highlight the need for continued research and advancements in this field. The future of atherosclerosis treatment holds promise with the exploration of factors that could potentially prove to be the underlying cause of atherosclerosis, particularly ongoing research into lipoprotein(a). Through ongoing innovation and collaboration, we strive to improve the prevention, management, and outcomes for individuals affected.
Seeking partners for atherosclerosis research? Connect with millions of patients through IMA Clinical Research’s growing, nationwide database.
References
- Slijkhuis W, Mali W, Appelman Y. A historical perspective towards a non-invasive treatment for patients with atherosclerosis. Neth Heart J. 2009 Apr;17(4):140-4. doi: 10.1007/BF03086236. PMID: 19421359; PMCID: PMC2669243.
- Minelli S, Minelli P, Montinari MR. Reflections on Atherosclerosis: Lesson from the Past and Future Research Directions. J Multidiscip Healthc. 2020;13:621-633 https://doi.org/10.2147/JMDH.S254016
- Gluba-Brzózka A, Franczyk B, Rysz-Górzyńska M, Ławiński J, Rysz J. Emerging Anti-Atherosclerotic Therapies. Int J Mol Sci. 2021 Nov 9;22(22):12109. doi: 10.3390/ijms222212109. PMID: 34829992; PMCID: PMC8624828.
- Hetherington, I., & Totary-Jain, H. (2022). Anti-atherosclerotic therapies: Milestones, challenges, and emerging innovations. Molecular Therapy, 30(10).
- Chen J, Zhang X, Millican R, Lynd T, Gangasani M, Malhotra S, Sherwood J, Hwang PT, Cho Y, Brott BC, Qin G, Jo H, Yoon YS, Jun HW. Recent Progress in in vitro Models for Atherosclerosis Studies. Front Cardiovasc Med. 2022 Jan 27;8:790529. doi: 10.3389/fcvm.2021.790529. PMID: 35155603; PMCID: PMC8829969.
