A novel role for calpain in the endothelial dysfunction induced by activation of angiotensin II type 1 receptor signaling.

Rationale: The cytosolic protease calpain has been recently implicated in the vascular remodeling of angiotensin II (Ang II) type 1 receptor (AT(1)R) signaling. The role of Ang II/AT(1)R/calpain signaling on endothelial function, an important and early determinant of vascular pathology, remains though totally unknown. Accordingly, we investigated the role of calpain in the endothelial dysfunction of Ang II.

Endothelial S100A1 modulates vascular function via nitric oxide.

S100A1, a Ca(2+)-binding protein of the EF-hand type, is known to modulate sarcoplasmic reticulum Ca(2+) handling in skeletal muscle and cardiomyocytes. Recently, S100A1 has been shown to be expressed in endothelial cells (ECs). Because intracellular Ca(2+) ([Ca(2+)](i)) transients can be involved in important EC functions and endothelial NO synthase activity, we sought to investigate the impact of endothelial S100A1 on the regulation of endothelial and vascular function.

Adiponectin deficiency increases leukocyte-endothelium interactions via upregulation of endothelial cell adhesion molecules in vivo.

This study reports on what we believe are novel mechanism(s) of the vascular protective action of adiponectin. We used intravital microscopy to measure leukocyte-endothelium interactions in adiponectin-deficient (Ad(-/-)) mice and found that adiponectin deficiency was associated with a 2-fold increase in leukocyte rolling and a 5-fold increase in leukocyte adhesion in the microcirculation. Measurement of endothelial NO (eNO) revealed that adiponectin deficiency drastically reduced levels of eNO in the vascular wall.

Hyperglycemia is a major determinant of albumin permeability in diabetic microcirculation: the role of mu-calpain.

Increased permeability to albumin is a well-known feature of diabetic microvasculature and a negative prognostic factor of vascular complications. The mechanisms responsible for loss of the physiological albumin barrier in diabetic organs remain only partially understood. We have recently demonstrated that the protease mu-calpain is activated in hyperglycemia, which causes endothelial dysfunction and vascular inflammation.