Detection of metals and metalloproteins in the plasma of stroke patients by mass spectrometry methods

Abstract

Stroke is the leading cause of disability in adults world-wide. Well-recognized environmental risk factors for stroke include hypertension, smoking, diabetes mellitus, atrial fibrillation and atherosclerosis. Ischemic stroke, which accounts for ~85% of all stroke, is mainly caused by either intracranial thrombosis or extracranial embolism; hemorrhagic stroke can be classified as either intracerebral hemorrhage (ICH) or subarachnoid hemorrhage (SAH). Metalloproteins and metals play key roles in epigenetic events in living organisms, including hypertension, the most important modifiable risk factor for stroke. For example, Zinc (Zn) is located in the catalytic site of angiotensin-converting enzyme (ACE), a component of the renin-angiotensin system which is important for blood pressure regulation., Cadmium, lead, selenium, calcium, magnesium, sodium, potassium and other metals are well recognized to be associated with stroke risk and prognosis. Concentrations of metalloproteins in the blood plasma are important factors in a number of diseases including iron overload (hemochromatosis) and copper overload (Wilson’s disease). Exposure to toxic metals and pollutants in the air, water or food can lead to altered metabolism, which may alter levels of metalloproteins in plasma. Metalloproteins may be important for disease diagnosis. Thus, this study sought to develop a method of detecting metals and metalloproteins levels for distinguishing stroke types. In search of these, different analytical techniques such as affinity chromatography, size exclusion chromatography (SEC), inductively coupled plasma mass spectrometry (ICPMS) and electrospray mass spectrometry (ESIMS) were used.

The Copper bis(thiosemicarbazone) Complex CuII(atsm) Is Protective Against Cerebral Ischemia Through Modulation of the Inflammatory Milieu

“…As previously mentioned, studies with human patients have suggested an imbalance in copper homeostasis after cerebral ischemia [11,12]. Elevated levels of copper were observed in the circulation of stroke patients in both studies, suggesting that copper is redistributed due to stroke-induced damage.…”

“…While copper homeostasis is disturbed in chronic neurodegenerative diseases such as Alzheimer's disease (AD) [10], little is known about copper homeostasis in acute ischemic stroke. Several years ago, Kodali et al reported an increase in the plasma copper concentrations of ischemic stroke patients [11]. This observation was supported by a recent paper demonstrating that serum levels of both total copper and copper loosely bound to small molecules are elevated in serum of ischemic stroke patients [12].…”

High Urinary Tungsten Concentration Is Associated with Stroke in the National Health and Nutrition Examination Survey 1999–2010

“…Previous studies have indicated that metal toxicity is involved in stroke etiology [17] . The OR for stroke was not attenuated following adjustment for cobalt (often considered to be the principle toxic agent) and molybdenum.…”

Apolipoprotein A-I and Paraoxonase-1 Are Potential Blood Biomarkers for Ischemic Stroke Diagnosis

“…Based on our prior findings 5 and supportive evidence in the literature, 6–16 we tested the following 6 potential biomarkers for their potential utility in stroke diagnosis: paraoxonase-1, matrix metalloproteinase (MMP)-3, MMP-9, apolipoprotein (Apo) A-I, Apo C-I, and Apo C-III.…”