COVID-19 Causes Vascular Fibrosis and Vascular Remodelling!

Medical News: The COVID-19 pandemic has left an indelible mark on global health, and its aftermath continues to unravel new medical challenges. Among these, vascular fibrosis and vascular remodeling have emerged as critical concerns. Researchers from the University of Glasgow, West of Scotland Heart and Lung Centre, and the Queen Elizabeth University Hospital-UK have delved deep into these phenomena, aiming to understand how the virus disrupts the vascular system.


Potential mechanisms of vascular remodelling post-COVID. COVID-19 viral entry is mediated by the angiotensin converting enzyme 2 (ACE2) receptor leading to upregulation of pathways implicated in inflammation, haemostasis activation and extracellular matrix turnover.

This Medical News report explores the intricate mechanisms by which COVID-19 impacts the Vascular system, leading to long-term complications. The findings highlight the need for innovative treatments to address these enduring effects, which impact millions worldwide.
 
COVID-19 and Persistent Health Challenges
COVID-19, caused by the SARS-CoV-2 virus, is known for its acute respiratory symptoms, but its long-term effects are equally concerning. Post-COVID-19 syndrome, or "long COVID," affects approximately 3.7% of those infected, translating to 145 million individuals globally. Studies indicate that even individuals who experienced mild or moderate initial symptoms may face persistent health issues. These include fatigue, cardiovascular complications, and systemic inflammation.
 
Persistent symptoms such as these often stem from vascular damage. Endothelial dysfunction, a hallmark of severe COVID-19, leads to systemic inflammation and organ damage. Vascular fibrosis - characterized by excessive collagen deposition and stiffening of blood vessels - is one of the long-term complications identified in patients recovering from COVID-19.
 
Mechanisms Behind Vascular Fibrosis
SARS-CoV-2 enters cells via the angiotensin-converting enzyme 2 (ACE2) receptor, which is widely expressed in various tissues, including blood vessels. This receptor’s binding triggers a cascade of inflammatory and fibrotic pathways. In severe cases, this response disrupts the balance between vascular injury and repair, leading to fibrosis.
 
The research sheds light on the biological underpinnings of this process. Inflammatory markers, such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and vascular endothelial growth factor (VEGF), are significantly elevated in COVID-19 patients. These markers contribute to vascular inflammation, endothelial damage, and extracellular matrix (ECM) remodeling - key drivers of vascular fibrosis.
 
Moreover, studies have identified upregulation of matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs), in post-COVID patients. These enzymes regulate ECM turnover, and their dysregulation exacerbates fibrosis. Human resistance arteries from COVID-19 patients also exhibit increased collagen deposition, as evidenced by enhanced u ptake of histological dyes such as aniline blue and picrosirius red.
 
Vascular Remodeling: A Double-Edged Sword
Vascular remodeling, a dynamic process involving changes in vessel structure and function, can be both adaptive and pathological. While it enables the body to respond to injury, chronic inflammation and fibrosis can result in maladaptive remodeling. In the context of COVID-19, this phenomenon manifests as increased vascular stiffness, impaired endothelial function, and altered blood flow.
 
The CISCO-19 study, a prospective investigation into cardiovascular outcomes among hospitalized COVID-19 patients, revealed striking findings. Myocardial scarring was detected in 54% of participants, while biomarkers of endothelial injury, such as intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), were elevated. These indicators highlight the pervasive vascular damage inflicted by the virus.
 
ACE2: The Central Player in Vascular Pathology
The ACE2 receptor plays a pivotal role in the vascular complications associated with COVID-19. By facilitating viral entry, it becomes a conduit for systemic inflammation and fibrosis. ACE2 deficiency, observed in severe COVID-19 cases, further exacerbates vascular stiffness and injury through unregulated angiotensin II activity. This peptide hormone promotes oxidative stress, apoptosis, and vascular smooth muscle cell dysfunction.
 
Interestingly, preclinical studies have demonstrated the protective role of ACE2 in non-COVID-19 contexts. Its activation can mitigate lung injury and reduce vascular fibrosis. However, in COVID-19, the virus’s direct interaction with ACE2 disrupts these protective mechanisms, leading to long-lasting vascular pathology.
 
Clinical Implications and Diagnostic Challenges
Diagnosing vascular fibrosis and remodeling in post-COVID patients is complex. Advanced imaging techniques, such as cardiovascular magnetic resonance (CMR) and endomyocardial biopsy (EMB), provide valuable insights but have limitations. EMB, considered the gold standard, is invasive and associated with risks.
 
Meanwhile, CMR studies have revealed nonischemic myocardial fibrosis in 30% of post-COVID patients, a prevalence far exceeding pre-pandemic levels.
 
Symptoms such as fatigue, exertional breathlessness, and chest pain are common in post-COVID patients. These are often linked to coronary microvascular dysfunction and subendocardial ischemia - conditions associated with vascular remodeling. Understanding these mechanisms is crucial for developing targeted interventions.
 
Potential Therapeutic Approaches
Addressing vascular fibrosis and remodeling requires a multifaceted approach. Current therapies focus on mitigating inflammation and fibrosis through pharmacological agents. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) have shown promise in reducing fibrosis by modulating the renin-angiotensin-aldosterone system (RAAS).
 
Emerging therapies, such as chimeric antigen receptor T-cell (CAR-T) treatments targeting fibroblast activation protein (FAP), offer new hope. Preclinical studies have demonstrated significant reductions in cardiac fibrosis in experimental models. Additionally, Rho-kinase (ROCK) inhibitors, which target pro-fibrotic signaling pathways, are being explored for their potential to improve vascular function and reduce fibrosis.
 
Conclusion: A Call for Continued Research
The findings from these studies underscore the profound impact of COVID-19 on the vascular system. Vascular fibrosis and remodeling not only contribute to long-term complications in post-COVID patients but also highlight the broader implications of systemic inflammation on cardiovascular health. Collaborative efforts among researchers, clinicians, and policymakers are essential to address these challenges.
 
Future research should prioritize longitudinal studies to track the progression of vascular fibrosis and remodeling in post-COVID populations. Integrating tissue-based analyses with clinical data will provide deeper insights into the mechanisms driving these conditions. Such efforts will pave the way for innovative treatments that alleviate the burden of long COVID and improve quality of life for affected individuals.
 
The study findings were published in the peer-reviewed journal: Infectious Medicine.
https://www.sciencedirect.com/science/article/pii/S2772431X24000613
 
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