Cytoskeletal mechanisms regulating vascular endothelial barrier function in response to acute lung injury

Abstract

Endothelial cells (EC) form a semi-permeable barrier between the interior space of blood vessels and the underlying tissues. In acute lung injury (ALI) the EC barrier is weakened leading to increased vascular permeability. It is widely accepted that EC barrier integrity is critically dependent upon intact cytoskeletal structure and cell junctions. Edemagenic agonists, like thrombin or endotoxin lipopolysaccharide (LPS), induced cytoskeletal rearrangement, and EC contractile responses leading to disruption of intercellular contacts and EC permeability increase. The highly clinically-relevant cytoskeletal mechanisms of EC barrier dysfunction are currently under intense investigation and will be described and discussed in the current review.

Keywords:

• acute lung injury
• barrier function
• cytoskeleton
• endothelial junctions
• thrombin
• pulmonary endothelium

Abbreviations:

• AJ, adherens junction
• ALI, Acute Lung Injury
• ARDS, Acute Respiratory Distress Syndrome
• CaD, caldesmon
• CPI-17, PKC potentiated inhibitory protein of 17 kDa
• EC, endothelial cells
• GJ, gap junction
• HSP-27, small heat shock actin-capping protein of 27 kDa
• IL, interleukin
• LPS, lipopolysaccharide
• MLC, myosin light chain
• MLCK, Ca²⁺/calmodulin (CaM) dependent MLC kinase
• MLCP, myosin light chain phosphatase
• MT, microtubules
• MYPT1, myosin phosphatase targeting subunit 1
• PKA, protein kinase A
• PKC, protein kinase C
• SM, smooth muscle
• TLR4, toll-like receptor 4
• TNFα, tumor necrosis factor α
• TJ, tight junction

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Funding

This manuscript was supported by grant PO1HL0101902 from the National Institute of Health and Extramural Success Award from the Georgia Regents University.