The epicardium is the outermost layer of the heart wall, serving as a protective covering for the muscular tissue beneath it. This thin membrane is the visceral layer of the serous pericardium, the inner layer of the sac surrounding the entire heart. It consists of a single sheet of flattened mesothelial cells resting on a layer of connective tissue. The epicardium’s unique position and cellular makeup are foundational to its diverse and complex roles in normal heart function and response to injury.
Anatomy and Position
The epicardium is directly adherent to the surface of the myocardium, the heart’s middle, muscular layer. It is immediately adjacent to the pericardial cavity, a space filled with fluid. Histologically, the membrane is defined by its outer layer of mesothelial cells and the underlying loose connective tissue. This sub-layer contains a variable amount of specialized fat known as epicardial adipose tissue (EAT).
Epicardial fat is a visceral fat depot that rests directly on the heart muscle without a layer of fascia separating the two tissues. EAT thickness varies across the heart, typically being most prominent along the grooves that house the major coronary arteries. This anatomical intimacy allows for direct exchange of substances between the fat, the vessels, and the underlying myocardium. The epicardium, along with the parietal layer of the serous pericardium, forms the boundary of the fluid-filled space that facilitates cardiac movement.
Essential Physiological Roles
In the adult heart, the epicardium functions as a protective and mechanical barrier. The mesothelial cells secrete a small volume of serous fluid, typically between 20 and 60 milliliters, into the pericardial cavity. This pericardial fluid acts as a lubricant, reducing the friction generated as the heart beats within the surrounding pericardial sac. This lubrication allows the heart to move freely and fully contract.
A primary role of the epicardium is to house the main coronary vasculature and cardiac nerves. The major coronary arteries and veins, which supply and drain the heart muscle, are embedded within the connective tissue layer of the epicardium before they branch and penetrate the myocardium. This location provides mechanical support and a cushioned environment for these large vessels. The epicardium also acts as a localized signaling center through the secretion of paracrine factors that regulate the function of the adjacent heart muscle and blood vessels.
Contribution to Cardiac Repair
The epicardium holds potential for cardiac repair because it harbors a reservoir of progenitor cells. These Epicardium-derived cells (EPDCs) are typically dormant in the healthy adult heart but can be reactivated following a severe cardiac injury, such as a myocardial infarction. Following injury, the epicardial cells undergo a process called epithelial-to-mesenchymal transition. In this process, the flattened epithelial cells detach from the membrane and transform into mobile, mesenchymal cells.
These newly formed EPDCs migrate from the heart’s surface into the injured myocardium. Their primary fate in the adult human heart is differentiation into cardiac fibroblasts, which lay down the collagen matrix that forms the scar tissue. This dense fibrotic scar is necessary to maintain the structural integrity of the damaged ventricular wall. EPDCs also differentiate into vascular smooth muscle cells and pericytes, which are necessary components for the formation of new blood vessels.
This regenerative response, known as neovascularization or angiogenesis, is supported by paracrine factors secreted by the epicardium, such as vascular endothelial growth factor (VEGFA) and fibroblast growth factor (FGF2). These factors stimulate the growth of a new microvascular network to supply blood to the surviving tissue. While the adult human epicardium’s repair mechanism results mostly in fibrosis, current research aims to enhance its potential to generate muscle cells for complete tissue restoration.
Common Conditions Affecting the Epicardium
The most common condition directly involving the epicardium is pericarditis, the inflammation of the pericardium. This inflammation causes the pericardial layers, including the epicardium, to rub against each other, leading to a characteristic sharp chest pain. The pain is often aggravated by taking a deep breath or lying down, and it may be alleviated by sitting up and leaning forward. Pericarditis is most frequently idiopathic, meaning the cause is unknown, but it is often attributed to viral infections, autoimmune disorders like lupus, or injury following a heart attack or surgery.
Epicardial adipose tissue (EAT) plays a role in cardiovascular health and disease. As a visceral fat depot, EAT is metabolically active and secretes a range of substances called adipokines. In healthy states, EAT may secrete protective factors, but in conditions associated with cardiovascular risk, it tends to overproduce pro-inflammatory cytokines. Due to the direct contact between EAT and the underlying coronary arteries, these inflammatory molecules are released locally, promoting the development of atherosclerosis and coronary artery disease. Increased volume or thickness of EAT is considered a risk factor linked to metabolic disease and adverse cardiac events.