Abstract
We discovered and validated medium sized apolipoprotein (a) as a marker for good myocardial collaterization. A total of 80 subjects were investigated in two serial studies: a discovery study (n=14) applying a pooling strategy to a gel and label free proteomics platform followed by a validation study (n=80) measuring apolipoprotein(a) isoforms and concentration in individual subjects. Degree of myocardial collaterization as well as apolipoprotein(a) concentration and isoform determination were performed by state-of-the-art methodologies. As apolipoprotein(a) concentration negatively correlates with isoform size (variable number of Kringle-IV type 2 repeats in human population), subjects were grouped into patients with small, medium and large apolipoprotein(a) isoforms for the statistical analysis. Among the 70 subjects with medium and large apolipoprotein(a) isoforms (>17 Kringle-IV type 2 repeats), subjects with insufficient collaterization (n=57) had a median apolipoprotein(a) concentration of 11.9 nmol/L, while patients with sufficient collaterization (n=13) had a median concentration of 31.3 nmol/L (p=0.033, Mann-Whitney U-test). Among the 52 subjects with medium sized apolipoprotein(a) isoforms (30 17) the difference in concentration was even more significant (13.4 vs 33.5 nmol/L, p=0.008).
Highlights
Blood vessels connecting left and right coronary arteries are referred to as “coronary collateral vessels” or “coro-J Proteomics BioinformVolume 1(8) : 389-400 (2008) - 389 ISSN:0974-276X JPB, an open access journal nary anastomoses”
The approach is limited to the ~120 most abundant proteins and is not capable to detect lower abundant proteins
The screen suggests a correlation between the degree of myocardial collaterization, represented by the collateral flow index (CFI) value, and the concentration of apo(a) in blood plasma
Summary
Blood vessels connecting left and right coronary arteries are referred to as “coronary collateral vessels” or “coro-J Proteomics BioinformVolume 1(8) : 389-400 (2008) - 389 ISSN:0974-276X JPB, an open access journal nary anastomoses”. The presence of sufficient collaterals to prevent ischemia during coronary occlusion can only be determined by invasive methods. It has been determined empirically that a CFI 0.25 is sufficient to prevent myocardial ischemia in the event of a one-minute coronary occlusion (Pohl et al, 2001). The response of collateral development to a certain obstructive stimulus (higher flow rates and high shear stress in preexisting interconnecting arterioles) is highly variable and it is adequate only in about 1/3 of patients with CAD to prevent myocardial ischemia during occlusion (Pohl et al, 2001). Angiogenesis and arteriogenesis are involved in enhancing the degree of collaterization The latter is thought of being the more important factor, as increasing the diameters of already existing arterioles contributes more to the blood supply than the formation of new capillaries. The attracted mononuclear blood cells together with the endothelium orchestrate the remodeling process, which includes cell proliferation, degradation and rebuilding of extra cellular matrix (Heil and Schaper, 2007)
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