Anti-MYLK (aa 1721-1734) polyclonal antibody

The importance of maintaining contractile function in aortic smooth muscle cells (SMCs) is evident by the fact that heterozygous mutations in the major structural proteins or kinases controlling contraction lead to the formation of aneurysms of the ascending thoracic aorta that predispose to life-threatening aortic dissections. Force generation by SMC requires ATP-dependent cyclic interactions between filaments composed of SMC-specific isoforms of a-actin (encoded by ACTA2) and myosin heavy chain (MYH11). ACTA2 and MYH11 mutations are predicted or have been shown to disrupt this cyclic interaction predispose to thoracic aortic disease. Movement of the myosin motor domain is controlled by phosphorylation of the regulatory light chain on the myosin filament, and loss-of-function mutations in the dedicated kinase for this phosphorylation, myosin light chain kinase (MYLK) also predispose to thoracic aortic disease. Finally, a mutation in the cGMP-activated protein kinase (PRKG1) results in constitutive activation of the kinase in the absence of cGMP, thus driving SMC relaxation in part through increased dephosphorylation of the regulatory light chain and predisposes to thoracic aortic disease. Furthermore, SMCs cannot generate force without connections to the extracellular matrix through focal adhesions, and mutations in the major protein in the extracellular matrix, fibrillin-1, linking SMCs to the matrix also cause thoracic aortic disease in individuals with Marfan syndrome. Thus, disruption of the ability of the aortic SMC to generate force through the elastin-contractile units in response to pulsatile blood flow may be a primary driver for thoracic aortic aneurysms and dissections.

Pacemaker lead-associated cardiac perforation is a rare phenomenon. Lead perforations can be acute, subacute, or chronic following lead placement. Symptoms are typically nonspecific and depend on the location of the displaced lead. Diagnostic workup requires interrogation of the pacemaker and imaging studies. Management of lead displacement is dependent on multiple risk factors such as age, gender, corticosteroid use, and anticoagulation therapy. A 74-year-old female with a history of myosin light chain kinase (MYLK) 2 hypertrophic cardiomyopathy, Sjogren's syndrome, Raynaud's disease, and sick sinus syndrome was evaluated for an abnormal finding on pacemaker interrogation. The patient's only symptom was tingling of her left breast. Imaging studies confirmed pacemaker lead perforation. Right ventricle perforation due to a pacemaker lead displacement can cause severe complications. Early identification and treatment by physicians can reduce the risk of mortality.