PAPPA as a Marker for Plaque Stability

The progression and destabilization of atheromatous plaques involve major changes in the structure ofthe arterial wall. Matrix metalloproteinases (MMPs) are potential indicators of arterial inflammation, and by degrading extracellular matrix, they contribute to the fragility of the lipid-rich, atherosclerotic plaque and finally to its rupture. PAPP-A is a high-molecular-weight, zinc-binding MMPs enzyme that is measured during pregnancy in maternal blood for the fetal diagnosis of Down syndrome. However, low levels of circulating PAPP-A are also physiologically present in both men and women. As previously described for several other MMPs (MMP-1, MMP-3, MMP-12, or MMP-13) (26, 27), data from patients with ACS also indicate the presence of PAPP-A in atherosclerotic plaques (28). Among patients who died suddenly from cardiac causes, PAPP-A was abundantly expressed in ruptured and eroded unstable plaques, but PAPP-A was absent or minimally expressed in stable plaques (28). In plaques with large lipid cores and cap rupture, staining for PAPP-A revealed that the enzyme occurred mostly in the inflammatory shoulder region. PAPP-A is a specific activator of insulin-like growth factor-1, a mediator of atherosclerosis, and has been implicated in coronary plaque disruption (29).

With respect to the prognostic impact of elevated PAPP-A levels in patients with ACS, a recent study suggests that measurement of plasma PAPP-A is an independent predictor of ischemic cardiac events and the need for revascularization in patients who present with suspected MI but remain troponin negative (Fig. 3) (30).

The endogenous inhibitor of PAPP-A, the proform of eosinophil major basic protein (proMBP), may also play an important role in the pathophysiology of ACSs. Indeed, to oo

Gambar Struktur Pembulu Darah

Fig. 2. Pathophysiology ofatherosclerosis with respect to lesion development, progression, and destabilization. A variety of biomarkers with distinct pathophysiological profiles can be used to assess disease activity. ICAM-1, intracellular adhesion molecule-1; VCAM-1, vascular cell adhesion molecule-1; HGF, hepatocyte growth factor; CKMB, creatine kinase-MB.

Fig. 2. Pathophysiology ofatherosclerosis with respect to lesion development, progression, and destabilization. A variety of biomarkers with distinct pathophysiological profiles can be used to assess disease activity. ICAM-1, intracellular adhesion molecule-1; VCAM-1, vascular cell adhesion molecule-1; HGF, hepatocyte growth factor; CKMB, creatine kinase-MB.

60 80 100 120 Days after enrollment

Fig. 3. Predictive value of PAPP-A in patients with ACS. Kaplan-Meier curves of event-free survival for the combined end points cardiovascular death, MI, and revascularization according to PAPP-A groups (n = 136) are shown.

Table 1

Multivariate Analysis for Prediction of Combined End Points Cardiovascular Death, MI, and Revascularization According to PAPP-A Groups (n = 136)

Table 1

Multivariate Analysis for Prediction of Combined End Points Cardiovascular Death, MI, and Revascularization According to PAPP-A Groups (n = 136)

Variable

r

p

B (95% CI)a

├čb

p

Age

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