July 10, 2008

On The Pursuit Of Arterial Plaques

arterial plaque affecting the brain and heartIn patients of disorders of lipid metabolism as in metabolic syndrome, diabetes mellitus and hypercholesterolemia, cholesterol laden plaques develop in the lumen of arteries. These plaques hinder the flow of blood leading to peripheral arterial disease (PAD). The narrowing of blood vessel that occur gives rise to symptoms of intermittent claudication and rest pain. Intermittent claudication is characterized by pain of the lower extremities as the person walks a few steps. This may progress to rest pain which is continually present, irrespective of whether the person walks or not. These plaques may also restrict blood flow to the heart causing myocardial ischemia.

What happens when these plaques rupture or loosen and detach? Fatal myocardial infarction (MI) and stroke (Cerebrovascular accident) may result when the heart or the brain arteries are involved respectively. We know that dyslipidemia of diabetes predispose us greatly to atherogenous plaque formation. LDL (low density lipoprotein), particularly oxidized LDL is a grave offender in this regard. Now imaging modalities are at hand which will let us visualize these atherosclerotic events, in real time.

Inflammation by oxidized LDL and their ilks increase the production of TNF-alpha (Tumor Necrosis Factor) and IL-1 (InterLeukin-1). They in turn increase the expression of
vascular cell adhesion molecule-1 (VCAM) and P selectin. These intracellular adhesion molecules kind of attract leukocytes, which bind loosely to the plaque. These are the ominous plaques seething to rupture and loosen.

Micro Particles of Iron Oxide (MPIO) targeted with anti-VCAM-1 monoclonal antibody (mAb) are now being used to probe and identify these lesions. While the monoclonal antibody will latch onto the antigen (VCAM) as a key fits onto a lock; the microparticles of iron will act as a marker when seen in NMR (Nuclear Magnetic Resonance) imaging. Also called MRI or magnetic resonance imaging, this technique detects the density and spins of protons (H+ or hydrogen nuclei). In areas where contrast is less, contrast agents are employed to get a clear picture. Now, a team from National Taiwan University has developed this technique which employs dextran-coated iron oxide nanoparticles tagged with anti-VCAM-1 to get a glimpse of whats going on inside arterial lumen. A combination of anti-VCAM-1 mAb and anti-P-selectin mAb (VCAM-MPIO-P-selectin) is also being developed.

Although we already have angiography, intravascular ultrasound, and optical coherence tomography to detect these plaques, the newer techniques will certainly throw more light on this insidious killer process within.

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