TY - JOUR

T1 - The endothelial border to health

T2 - Mechanistic evidence of the hyperglycemic culprit of inflammatory disease acceleration

AU - Hansen, Nina Wærling

AU - Hansen, Anker Jon

AU - Sams, Anette

PY - 2017/3

Y1 - 2017/3

N2 - The endothelial cell (EC) layer constitutes a barrier that controls movements of fluid, solutes and cells between blood and tissue. Further, the endothelial layer regulates vascular tone and directs local humoral and cellular inflammatory processes. The strategic position makes it an important player for maintenance of health and for development of a number of diseases. Endothelial dysfunction is known to be an important component of type 2 diabetes, but is also assumed to be involved in many other diseases, for example, rheumatoid arthritis, inflammatory bowel disease, asthma, and cardiovascular diseases. We here suggest that the EC plays a pivotal role in disease pathophysiology through initiation, potentiation, and maintenance of several inflammatory mechanisms. Our contention is based on the observation that hyperglycemia—intermittent or sustained, local or systemic—is a major culprit for several endothelial dysfunctions. There is also mounting epidemiological evidence that dietary intake of refined sugars is important for the development of a number of diseases beyond obesity and type 2 diabetes. Various diseases involving inflammatory and immunological components are accelerated by hyperglycemic events because the endothelium transduces “high glucose” signaling into significant pathophysiological phenomena leading to reduced endothelial barrier function, compromised vascular tone regulation and inflammation (e.g., cytokine secretion and RAGE activation). In addition, endothelial extracellular proteins form epitopes for potential specific antibody formation upon interactions with reducing sugars. This paper reviews the endothelial metabolism, biology, inflammatory processes, physical barrier functions, and summarizes evidence that although stochastic in nature, endothelial responses to hyperglycemia are major contributors to disease pathophysiology. We present molecular and mechanistic evidence that both biological and physical barriers, protein function, specific immunity, and inflammatory processes are compromised by hyperglycemic events and thus, hyperglycemic events alone should be considered risk factors for numerous human diseases.

AB - The endothelial cell (EC) layer constitutes a barrier that controls movements of fluid, solutes and cells between blood and tissue. Further, the endothelial layer regulates vascular tone and directs local humoral and cellular inflammatory processes. The strategic position makes it an important player for maintenance of health and for development of a number of diseases. Endothelial dysfunction is known to be an important component of type 2 diabetes, but is also assumed to be involved in many other diseases, for example, rheumatoid arthritis, inflammatory bowel disease, asthma, and cardiovascular diseases. We here suggest that the EC plays a pivotal role in disease pathophysiology through initiation, potentiation, and maintenance of several inflammatory mechanisms. Our contention is based on the observation that hyperglycemia—intermittent or sustained, local or systemic—is a major culprit for several endothelial dysfunctions. There is also mounting epidemiological evidence that dietary intake of refined sugars is important for the development of a number of diseases beyond obesity and type 2 diabetes. Various diseases involving inflammatory and immunological components are accelerated by hyperglycemic events because the endothelium transduces “high glucose” signaling into significant pathophysiological phenomena leading to reduced endothelial barrier function, compromised vascular tone regulation and inflammation (e.g., cytokine secretion and RAGE activation). In addition, endothelial extracellular proteins form epitopes for potential specific antibody formation upon interactions with reducing sugars. This paper reviews the endothelial metabolism, biology, inflammatory processes, physical barrier functions, and summarizes evidence that although stochastic in nature, endothelial responses to hyperglycemia are major contributors to disease pathophysiology. We present molecular and mechanistic evidence that both biological and physical barriers, protein function, specific immunity, and inflammatory processes are compromised by hyperglycemic events and thus, hyperglycemic events alone should be considered risk factors for numerous human diseases.

KW - advanced glycation end-product

KW - endothelial cell

KW - epitopes

KW - hyperglycemia

KW - inflammation

KW - oxidative stress

KW - protein glycation

U2 - 10.1002/iub.1610

DO - 10.1002/iub.1610

M3 - Review

C2 - 28230336

AN - SCOPUS:85013774465

VL - 69

SP - 148

EP - 161

JO - IUBMB Life

JF - IUBMB Life

SN - 1521-6543

IS - 3

ER -