Cardiovascular disorders

Diastolic heart failure; Restrictive cardiomyopathy; Frozen shoulder

Diastolic heart failure is a cardiovascular disease characterized by the funtional decline in either the left ventricle or both ventricles during diastole. Diastolic heart failure can be caused by any process that leads to the stiffening fo the left ventricle, including hypertension, aortic stenosis, diabetes, constrictive pericarditis, restrictive cardiomyopathy. Restrictive cardiomyopathy is a heart disease characterized by rigid walls of the heart, restricting the stretching of the heart and thus the ability of the heart chamber to completely fill with blood. Frozen shoulder, also known as adhesive capsulitis, is a disease characterized by the inflammation of the connective tissue surrounding the shoulder, resulting in the restriction of movement of the glenohumeral joint of the shoulder. High levels of JNK phosphorylation have been observed in tissue samples from abdominal aortic aneurysm patients. In rat aortic vascular smooth muscle cells, JNK induces the expression of genes that promote the degradation of the extracellular matrix (ECM), while suppressing enzymes that synthesize ECM components, such as Lox and Plod1. Therefore, JNK is involved in the pathogenesis of disorders of the cardiovascular system as it acts to promote abnormal ECM metabolism. Activation of the stress-activated MAP kinases, particularly JNK and p38, are associated with different forms of cardiac pathology, specifically related to the role of the proteins in the regulation of hypertrophy and apoptosis. Increased JNK activity has been correlated with heart failure, specifically at the onset of stress stimulation. in this context, JNK may function to promote cardiomyocyte hypertrophy and apoptotic cell death. In addition, JNK activity has been linked to different aspects of cardiac pathology, including contractile dysfunction, extracellular matrix remodelling, communication between cardiomyocytes, and cardiac metabolic regulation.
 

TranscriptoNET (www.transcriptonet.ca) analysis with mRNA expression data retrieved from the National Center for Biotechnology Information's Gene Expression Omnibus (GEO) database, which was normalized against 60 abundantly and commonly found proteins, indicated altered expression for this protein kinase as shown here as the percent change from normal tissue controls (%CFC) as supported with the Student T-test in the following types of human cancers: Bladder carcinomas (%CFC= -52, p<0.0001); Brain glioblastomas (%CFC= +113, p<0.1); Cervical cancer stage 1B (%CFC= +385); Clear cell renal cell carcinomas (cRCC) stage I (%CFC= +384, p<0.0001); andProstate cancer - primary (%CFC= +48, p<0.0001). The COSMIC website notes an up-regulated expression score for JNK1 in diverse human cancers of 328, which is 0.7-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 152 for this protein kinase in human cancers was 2.5-fold of the average score of 60 for the human protein kinases.

Insertional mutagenesis studies in mice support a role for this protein kinase in mouse cancer oncogenesis.

Percent mutation rates per 100 amino acids length in human cancers: 0.07 % in 25587 diverse cancer specimens. This rate is only -2 % lower and is very similar to the average rate of 0.075 % calculated for human protein kinases in general.

Highest percent mutation rates per 100 amino acids length in human cancers: 0.54 % in 1093 large intestine cancers tested; 0.43 % in 602 endometrium cancers tested; 0.32 % in 805 skin cancers tested.

None > 4 in 20,845 cancer specimens

Only 1 deletion, and no insertions or complex mutations are noted on the COSMIC website.