A NEW REVOLUTIONARY TEST PANEL FOR CARDIOVASCULAR, EPITHELIAL, AND CANCER DISEASES

 

Methylated Arginine, such as asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), are the products of posttranslational methylation of protein.

ADMA, one of the methylated form of the amino acid Arginine (Arg), is an endogenous inhibitor of the production of nitric oxide (NO) from arginine by nitric oxide synthase (NOS). It is one of the marker of endothelial disfunction. There is another closely related compound, a stereoisomer of ADMA, symmetric dimethylarginine (SDMA), which does not inhibit NOS, but may compete with arginine for cellular uptake, thereby limiting substrate availability of NOS, is known as an endogenous marker of renal function. A modest impairment of renal function has been recognized as a cardiovascular risk factor.

In contrast to ADMA and SDMA, homoarginine (hArg) a methylene (CH2) homologue of Arg, which has an additional CH2- group in carbon chain, is also known as a substrate of NOS. hArg may increase the availability of NO in two different ways: (1) hArg itself serves as a precursor of NO, (2) it potentially increases the intracellular concentration of L-Arginine, the substrate for NOS, by inhibiting the enzyme arginase which competes with NOS. Thus, hArg is positively related to endothelial function.

ADMA

Elevated plasma levels of ADMA strongly suggest the possibility of cardiovascular disease, endothelial dysfunction and most importantly various types of cancers such as breast cancer, colon cancer, lung cancer, and gastric cancer. Besides, in patients with hematopoietic tumor, atherosclerosis, hypertension and type II  diabetes have also shown high levels of ADMA. Young adults with chronic CT coronary artery calcification and high levels of ADMA have much higher incidence of stroke like episodes.

SDMA

Plasma SDMA is an early biomarker of progressive kidney failure. It reflects glomerular filtration rate (GFR) most sensitively and accurately, and was added to the International Renal Interest Society (IRIS) CKD guidelines to complement creatinine testing. The endogenous biomarker, creatinine, has poor sensitivity and specificity and is affected by extra-renal factors such as age, gender, diet, muscle man and medication. The levels of SDMA increase earlier in CKD, with an average of 40-50% reduction of GFR whereas in case of increased level of creatinine it requires at least 70-80% reduction of GFR. Also unlike creatinine SDMA is not affected by lean body mass. In our laboratory using LC MSMS methodology we have established that the increase levels of SDMA is positively correlated with reduced GFR.

Homoarginine

Unlike high level of ADMA and SDMA, low levels of plasma homoarginine (hArg) have been shown to correlate with adverse cardiovascular outcome. These low levels have also been found in diabetic patients on hemodialysis, patients with peripheral arterial disease, patients after ischemic stroke, patients referred for coronary angiography, and in renal transplant recipients.

 

Today ADMA, SDMA and hArg levels in plasma are measured in an automated platform using either very manual technique like ELISA or Liquid Chromatography coupled with single mass detection.  In our laboratory this panel is performed using UPLC /MSMS technique which provides higher specificity, sensitivity, and reproducibility along with short analysis runtime. 

 

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