Are there Angiotensin-Converting Enzyme 2 (ACE2) receptors in the human lung?

From the Guidelines

Yes, there are Angiotensin-Converting Enzyme 2 (ACE2) receptors in the human lung. ACE2 receptors are widely distributed throughout the respiratory tract, with significant expression in the epithelial cells lining the alveoli, bronchi, and trachea [ 1 ]. These receptors play an important physiological role in the renin-angiotensin system by converting angiotensin II to angiotensin 1-7, which has vasodilatory and anti-inflammatory effects. The presence of ACE2 receptors in lung tissue has gained particular attention during the COVID-19 pandemic because they serve as the primary entry point for SARS-CoV-2, the virus that causes COVID-19 [ 1 ].

Key Points

• The virus's spike protein binds to these receptors, enabling viral entry into host cells.
• The abundance of ACE2 receptors in the lungs partially explains why respiratory symptoms are prominent in COVID-19 infections.
• Understanding the distribution and function of these receptors has been crucial for developing therapeutic approaches targeting the virus-receptor interaction.
• The alveolar epithelium and capillary endothelium express ACE2, which may mediate COVID-19-related lung injury [ 1 ].
• SARS-CoV-2 infection of epithelial cells and subsequent viral proliferation likely exacerbates alveolar wall destruction and diffuse alveolar damage.
• Viral-induced ACE2 suppression is thought to propagate this acute lung injury by leading to increased lung Ang II content [ 1 ]. The presence of ACE2 receptors in the human lung is a critical factor in the pathogenesis of COVID-19, and understanding their role is essential for developing effective therapeutic strategies.

From the Research

ACE2 Receptors in the Human Lung

• The presence of Angiotensin-Converting Enzyme 2 (ACE2) receptors in the human lung is supported by several studies 2, 3, 4.
• ACE2 is highly expressed in the lungs, particularly in bronchial and alveolar epithelial cells, and plays a crucial role in the renin-angiotensin-aldosterone system (RAAS) 3.
• The expression of ACE2 in the lungs is increased in patients with comorbidities associated with severe COVID-19, such as hypertension, diabetes, and chronic obstructive lung disease 4.
• The ACE2 receptor is the primary entry point for SARS-CoV-2 into host cells, and its overexpression in certain individuals may make them more susceptible to COVID-19 infection 5.

Expression and Regulation of ACE2 in the Lung

• The expression of ACE2 in the lung can be influenced by various factors, including inflammation, comorbidities, and treatment with certain drugs 2, 4.
• Dexamethasone, a steroid commonly used to treat COVID-19, can increase the expression of ACE2 in lung epithelial cells, potentially affecting the entry of SARS-CoV-2 into host cells 2.
• Other studies have identified potential regulators of ACE2 in the human lung, including genes related to histone modifications 4.

Clinical Implications of ACE2 Expression in the Lung

• The expression of ACE2 in the lung has important implications for the treatment and management of COVID-19, particularly in patients with comorbidities or those receiving certain medications 3, 5.
• The use of recombinant soluble ACE2 in combination with remdesivir has been shown to improve the therapeutic effect against SARS-CoV-2 infection in vitro 6.