Sulfhydryl compounds influence immunoreactivity, structure and functional aspects of lipoprotein (a)

Lp(a) Particles Mold Fibrin-Binding Properties of Apo(a) in Size-Dependent Manner

“…The study of other apo(a) phenotypes derived from reduced Lp(a) particles is hampered by the risk of severely affecting the LBS structure and function by sulfhydryl groups. 43 Our data suggest that the fibrin affinity of small-sized apo(a) isoforms is preserved in Lp(a), whereas the affinity for fibrin of high-molecular-mass isoforms (Ͼ22 kringles) is reduced in a size-dependent manner in the Lp(a) particle. We hypothesize, in agreement with Klezovitch et al, 8 that interactions of apo(a) kringles with components of the Lp(a) particle may contribute to the observed changes in fibrin affinity.…”

Apolipoprotein(a) inhibits the conversion of Glu‐plasminogen to Lys‐plasminogen: a novel mechanism for lipoprotein(a)‐mediated inhibition of plasminogen activation

“…Indeed, several in vitro and in vivo studies have shown that Lp(a)/apo(a) can inhibit fibrin clot lysis [11][12][13], as well as tissue-type plasminogen activator (tPA)-mediated plasminogen activation on the surface of fibrin [14][15][16][17]. However, the mechanism by which apo(a) inhibits tPA-mediated plasminogen activation has been controversial, with both competitive [14] and uncompetitive [15,16] mechanisms invoked to describe the observed inhibition. More recently, we developed an equilibrium template model to describe the inhibitory mechanism [17].…”

Vitamin Intervention for Stroke Prevention Trial

“…2 Mechanisms by which tHcy may cause vascular disease include propensity for thrombosis and impaired thrombolysis, [3][4][5][6] increased production of hydrogen peroxide, 7 endothelial dysfunction, 8 -11 and increased oxidation of low-density lipoprotein and lipoprotein(a). 12 Vitamin therapy with folate, pyridoxine (B 6 ), and cobalamin (B 12 ) reduces tHcy 13 and reverses endothelial dysfunction induced by high tHcy. 8,10 Therefore, we conducted the Vitamin Intervention for Stroke Prevention (VISP) trial to determine whether treatment with high-dose vitamin therapy (2.5 mg folate, 25 mg B 6 , and 400 mcg B 12 daily) significantly reduced stroke and the combined end point of stroke, death, and myocardial infarction compared with low-dose vitamin therapy (20 mcg folate, 200 mcg B 6 , and 6 mcg B 12 ).…”

“…12 Vitamin therapy with folate, pyridoxine (B 6 ), and cobalamin (B 12 ) reduces tHcy 13 and reverses endothelial dysfunction induced by high tHcy. 8,10 Therefore, we conducted the Vitamin Intervention for Stroke Prevention (VISP) trial to determine whether treatment with high-dose vitamin therapy (2.5 mg folate, 25 mg B 6 , and 400 mcg B 12 daily) significantly reduced stroke and the combined end point of stroke, death, and myocardial infarction compared with low-dose vitamin therapy (20 mcg folate, 200 mcg B 6 , and 6 mcg B 12 ). In the main analysis, which was an intention-to-treat analysis, the difference in outcomes was very small, and the study was stopped because of futility.…”

“…The study vitamin in both arms included the recommended daily intake (RDI) of all vitamins other than folate/B 6 /B 12 . Because of concern about subacute combined degeneration and neuropathy, we included the RDI for B 12 in the low-dose arm. In both the high-dose and low-dose arms of the study, patients with low levels of B 12 (Ͻ150 pmol/L) received B 12 injections to prevent neurological complications.…”