Capillary rarefaction: a missing link in renal and cardiovascular disease?

Patients with chronic kidney disease (CKD) have an increased risk for cardiovascular morbidity and mortality. Capillary rarefaction may be both one of the causes as well as a consequence of CKD and cardiovascular disease. We reviewed the published literature on human biopsy studies and conclude that renal capillary rarefaction occurs independently of the cause of renal function decline. Moreover, glomerular hypertrophy may be an early sign of generalized endothelial dysfunction, while peritubular capillary loss occurs in advanced renal disease. Recent studies with non-invasive measurements show that capillary rarefaction is detected systemically (e.g., in the skin) in individuals with albuminuria, as sign of early CKD and/or generalized endothelial dysfunction. Decreased capillary density is found in omental fat, muscle and heart biopsies of patients with advanced CKD as well as in skin, fat, muscle, brain and heart biopsies of individuals with cardiovascular risk factors. No biopsy studies have yet been performed on capillary rarefaction in individuals with early CKD. At present it is unknown whether individuals with CKD and cardiovascular disease merely share the same risk factors for capillary rarefaction, or whether there is a causal relationship between rarefaction in renal and systemic capillaries. Further studies on renal and systemic capillary rarefaction, including their temporal relationship and underlying mechanisms are needed. This review stresses the importance of preserving and maintaining capillary integrity and homeostasis in the prevention and management of renal and cardiovascular disease.

A disintegrin and metalloproteases: molecular scissors in angiogenesis, inflammation and atherosclerosis.

A disintegrin and metalloproteases (ADAMs) are enzymes that cleave (shed) the extracellular domains of various cell surface molecules, e.g. adhesion molecules, cytokine/chemokine and growth factor receptors, thereby releasing soluble molecules that can exert agonistic or antagonistic functions or serve as biomarkers. By functioning as such molecular scissors, ADAM proteases have been implicated in various diseases, e.g. cancer, and their role in cardiovascular diseases is now emerging. This review will focus on the role of ADAM proteases in molecular mechanisms of angiogenesis and inflammation in relation to atherosclerosis. Besides a concise overview of the current state and recent advances of this research area, we will discuss key questions about redundancy, specificity and regulation of ADAM proteases and emphasize the importance of confirmation of in vitro findings in in vivo models.