Pericytes and Its Clinical Implications

Introduction:

Pericytes are special cells in tiny blood vessels that work closely with endothelial cells lining the vessels. They were first identified by Eberth in 1865, and since then, scientists have been studying them a lot because they do many important things for blood vessels and tissues. Recent discoveries about pericytes have shown that they play a key role in different processes in the body, both normal and when things go wrong. This new knowledge has important implications for medical treatments.

What Are Pericytes?

Pericytes are cells that can be observed along the walls of small blood vessels, such as capillaries and post-capillary venules. In the central nervous system (CNS), they play a crucial role in forming blood vessels, maintaining the blood-brain barrier, regulating immune cell entry into the CNS, and controlling blood flow in the brain. In the past, people thought that when brain cells were active, the increased blood flow happened because the muscles around small blood vessels (arterioles) relaxed. But now, recent discoveries show that a lot of this increased blood flow actually comes from the widening of tiny blood vessels called capillaries. This happens because special cells called pericytes relax, not the arterioles. Pericytes are also important in diseases like ischemia, where they squeeze capillaries, trapping blood cells and making it harder for blood to flow after a clot is removed in a stroke. This explains how important pericytes are as a target for treatments.

What Are the Functions of Pericytes?

The main functions of pericytes are mentioned below :

• Vascular Stability: Pericytes are integral to the structural stability of blood vessels. They provide physical support and regulate the contractility of the vessel walls, helping to maintain the integrity of the vascular network. This involvement in vascular stability is crucial for preventing leakage and ensuring proper blood flow.

• Regulation of Blood Flow: Pericytes actively participate in the regulation of blood flow within capillaries. They can constrict or dilate their coverage area, influencing the diameter of capillaries and, consequently, blood flow. This dynamic control contributes to the distribution of blood within tissues according to metabolic demand.

• Angiogenesis: These cells play an important role in angiogenesis, the process of forming new blood vessels from pre-existing ones. They secrete growth factors and cytokines, promoting the proliferation and migration of endothelial cells, as well as the formation of new capillaries. This collaboration between pericytes and endothelial cells is vital during development, tissue repair, and wound healing.

• Vascular Permeability: Pericytes contribute to the maintenance of vascular permeability by interacting with endothelial cells. They help regulate the passage of molecules and cells across the endothelial barrier. This influences the exchange of oxygen, nutrients, and some waste products between the blood and surrounding tissues.

• Blood-Brain Barrier Function: In the central nervous system, pericytes are essential components of the blood-brain barrier (BBB). They actively participate in regulating the permeability of the BBB, controlling the entry of substances from the bloodstream into the brain. This function is crucial for maintaining the unique microenvironment of the brain.

• Tissue Repair and Fibrosis: Pericytes contribute to tissue repair and regeneration by participating in fibrosis and scar tissue formation.

• Immunomodulation: Pericytes are involved in modulating the immune response within tissues. They can influence the immune cell activation and recruitment, which helps control inflammation. Dysfunction in pericyte-mediated immunomodulation is implicated in various inflammatory conditions and diseases.

• Neurovascular Coupling: In the brain, pericytes contribute to neurovascular coupling, a mechanism that ensures adequate blood supply to active neuronal regions. They respond to neural activity by regulating blood flow, contributing to the coordination of neuronal and vascular responses.

• Regulation of Extracellular Matrix: Pericytes are involved in maintaining the integrity of the extracellular matrix within blood vessel walls. They contribute to the synthesis and remodeling of extracellular matrix components, influencing tissue structure and function.

What Are the Clinical Implications of Pericytes?

Pericytes can be influenced by various conditions and factors that impact their function and behavior. The following are several conditions affecting pericytes:

• Diabetes: The retina has the highest concentration of pericytes in the body. Diabetic individuals are at risk of developing diabetic retinopathy, and one of the early signs is the reduction of pericytes in the retina. This decline, known as ‘pericyte dropout,’ is thought to be caused by persistently elevated blood sugar levels. The consequences are significant because they cause blood vessel walls to weaken and lead to the formation of tiny bulges called microaneurysms. Studies of these microaneurysms reveal a consistent lack of pericytes, suggesting that the absence of these cells may make the vessels more susceptible to aneurysms, posing a risk to their integrity.

• Neurological Disorders: Neurological disorders, such as Alzheimer's disease and stroke, can affect pericytes in the brain. Dysregulation of pericyte function has been implicated in the breakdown of the blood-brain barrier, contributing to neurovascular dysfunction and cognitive impairment. In chronic neurodegenerative diseases like Alzheimer's, the breakdown or malfunction of pericytes has been linked to the development of the disease. This pericyte degeneration is not exclusive to Alzheimer's, as recent reports indicate pericyte loss and dysfunction in other neurodegenerative disorders.

• Cancer: Tumors can influence pericyte behavior to promote angiogenesis and support tumor growth. Pericyte coverage of blood vessels within tumors may be altered, impacting vessel stability and promoting abnormal angiogenesis. Pericytes in tumors seem to be less firmly connected to blood vessels, and their extensions can reach into the tumor tissue. In certain tumor tissues, they also appear to be less numerous compared to the corresponding normal tissue. Targeting pericytes has become a focus in anti-angiogenic cancer therapies.

• Cardiovascular Diseases: Conditions like atherosclerosis and hypertension can affect pericytes in blood vessels. Pericyte dysfunction is associated with vascular instability, impaired blood flow regulation, and increased risk of cardiovascular events.

• Inflammatory Conditions: Chronic inflammatory conditions can influence pericyte behavior. Inflammation may lead to the activation of pericytes and their involvement in tissue fibrosis. Conversely, pericytes can modulate inflammation by influencing the recruitment and activity of immune cells.

• Aging: Aging is associated with changes in the microvasculature, including alterations in pericyte density and function. Age-related decline in pericyte coverage may contribute to impaired tissue perfusion and increased susceptibility to vascular diseases.

• Ischemia and Hypoxia: Conditions characterized by insufficient blood supply, such as ischemia and hypoxia, can impact pericytes. In response to low oxygen levels, pericytes may undergo phenotypic changes and contribute to tissue remodeling and repair.

• Genetic Mutations: Genetic mutations can lead to inherited conditions affecting pericytes. These mutations may impact pericyte development, function, or their ability to interact with endothelial cells, resulting in vascular abnormalities and associated disorders.

• Trauma and Injury: Trauma or injury to tissues can affect pericytes as they actively participate in the repair and regeneration processes. Pericytes may undergo differentiation into myofibroblasts, contributing to scar tissue formation and tissue remodeling.

• Metabolic Disorders: Metabolic disorders like obesity and metabolic syndrome that might affect pericyte function. In conditions like obesity, changes in adipose tissue vasculature involving pericytes may contribute to inflammation and metabolic dysfunction.

• Toxic Exposures: Exposure to certain toxins, drugs, or environmental factors can impact physical health. Toxic substances may induce cellular stress, leading to pericyte dysfunction and contributing to vascular complications.

Conclusion:

Pericytes, once seen as providing structural support to blood vessels, are now recognized as important contributors to both normal and disease-related processes. Their role in maintaining consistent blood vessels, promoting the formation of new blood vessels, and also aiding in tissue repair has significant implications for medical treatment. It is crucial to understand the complex interactions between pericytes and other cell types in various tissues to provide accurate therapies for a wide range of conditions (cancer, neurological disorders, and complications related to diabetes). Ongoing research in pericyte biology offers the potential to discover innovative treatment strategies and enhance patient outcomes in diverse areas of medicine.