Stress testing at the cellular and molecular level to unravel cellular dysfunction and growth factor signal transduction defects: What Molecular Cell Biology can learn from Cardiology

Abstract

SummaryClinical medicine has been revolutionized by the impact of cellular and molecular biology in the past 30 years. This article focuses on a novel approach, whereby the clinically proven and important concept of patient or organ stress testing is being applied to cellular models, thereby developing and validating novel quantitative molecular and cellular stress tests. One example is monocyte chemotaxis analysis, whereby circulating monocytes freshly isolated from peripheral blood are being tested for their migratory responsiveness towards relevant biological stimuli such as growth factors or chemokines. These stimuli are relevant for recruiting monocytes to sites of local inflammation such as during wound healing or arteriogenesis, i.e. growth of collateral arteries. Initial clinical studies to validate “ligand-induced monocyte chemotaxis” indicate that this parameter is impaired in the presence of various cardiovascular risk factors including diabetes mellitus, hypercholesterolemia or smoking. In addition, there is proof of concept that impaired monocyte chemotaxis is reversible as shown for anti-oxidants in smokers. Moreover, the parameter “ligand-induced monocyte chemotaxis” is of great relevance for basic science (including Molecular Cell Biology) as unravelling the underlying molecular mechanisms of cellular dysfunction will certainly stimulate our understanding of the molecular basis of cellular function. This article highlights the concept of stress testing in modern medicine. Cellular stress testing is introduced as a novel and intriguing approach, which was developed as bedside-to-bench. Future prospective clinical trials will have to validate the predictive value of cellular stress testing.