Endothelial Damage in Sepsis: The Importance of Systems Biology

Abstract

The early diagnosis and appropriate stratification of sepsis continues to be one of the most important challenges in modern medicine. Single isolated biomarkers have not been enough to improve diagnostic and prognostic strategies and to progress toward therapeutic goals. The information generated by the human genome project has allowed a more holistic approach to the problem. The integration of genomics, transcriptomics, proteomics and metabolomics in sepsis has allowed us to progress in the knowledge of new pathways which are pathophysiologically involved in this disease. Thus, we have understood the importance of and complex interaction between the inflammatory response and the endothelium. Understanding the role of important parts of the microcirculation, such as the endothelial glycocalyx and its interaction with the inflammatory response, has provided early recognition elements for clinical practice that allow the rational use of traditional medical interventions in sepsis. This comprehensive approach, which differs from the classical mechanistic approach, uses systems biology to increase the diagnostic and prognostic spectrum of endothelial damage biomarkers in sepsis, and to provide information on new pathways involved in the pathophysiology of the disease. This, in turn, provides tools for perfecting traditional medical interventions, using them at the appropriate times according to the disease's pathophysiological context, while at the same time discovering new and improved therapeutic alternatives. We have the challenge of transferring this ideal scenario to our daily clinical practice to improve our patients' care. The purpose of this article is to provide a general description of the importance of systems biology in integrating the complex interaction between the endothelium and the inflammatory response in sepsis.

Capillary refill time in sepsis: A useful and easily accessible tool for evaluating perfusion in children

“…It tends to be correlated with elevated lactate and multiple organ failure. In fact, microcirculation and endothelial abnormalities are considered to be the common denominator in multiple organ dysfunction syndrome in sepsis, as mentioned previously ( 8 , 12 , 15 ).…”

“…Recent studies suggest that microcirculatory and endothelial abnormalities are the common basis of organ failure in sepsis ( 14 ). In septic conditions, the accumulation of proteases accelerates endothelial glycocalyx degradation, resulting in increased leucocyte adhesion to the vessel wall, increased vascular permeability and intravascular coagulation ( 15 ). This whole response leads to a profound disruption of tissue perfusion.…”

The relationship between hematocrit and serum albumin levels difference and mortality in elderly sepsis patients in intensive care units—a retrospective study based on two large database

“…In addition to these, the depletion produced by the hypermetabolic state of sepsis patients and the gastrointestinal dysfunction can lower the level of ALB [ 39 ]. When the patient's plasma albumin decreases due to the above-mentioned various factors, the plasma colloid osmotic pressure in turn will decrease, a large amount of liquid will be retained in the interstitial space [ 40 ], and the effective circulating blood volume will be further reduced, red blood cells will aggregate, blood viscosity will increase, and microcirculation disorders will be aggravated [ 41 , 42 ]. It can lead to organ ischemia and focal necrosis, which can lead to organ failure and aggravate the condition of sepsis patients if it is severe or lasts for a long time [ 43 ].…”

Vasoactive Endothelial Growth Factor and Heat Shock Protein Gene Expression Response in Kawasaki Disease

“…Detailed downstream analysis for the validation of physical mechanisms is required to confirm biological processes. However, one advantage of the transcriptomic approach adopted is that it provides a systems-level view of multiple processes aiding an integrated understanding of complex biological processes 25 . Another issue in KD studies is the lack of temporal gene-sampling.…”