Constitutive expression of pregnancy-associated plasma protein-A in arterial smooth muscle reduces the vascular response to injury in vivo

Bale, Laurie K.; Resch, Zachary T.; Harstad, Sara L.; Overgaard, Michael Toft; Conover, Cheryl A.

doi:10.1152/ajpendo.00376.2012

Cited by 11 publications

(4 citation statements)

References 33 publications

(58 reference statements)

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“…The reasons for these apparently discrepant findings are unclear. There are likely to be differences in acute response to injury and chronic modulation of expression and signaling (Bale et al, 2013; Clemmons, 2007). And it is possible that reduced IGF signaling in pluripotent stem cells residing in skeletal muscle protects against premature depletion (Ratajczak et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Comparative gene expression and phenotype analyses of skeletal muscle from aged wild-type and PAPP-A-deficient mice

Conover

Bale

Nair

2016

Experimental Gerontology

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SUMMARY Mice deficient in pregnancy-associated plasma protein-A (PAPP-A) have extended lifespan associated with decreased incidence and severity of degenerative diseases of age, such as cardiomyopathy and nephropathy. In this study, the effect of PAPP-A deficiency on aging skeletal muscle was investigated. Whole-genome expression profiling was performed on soleus muscles from 18-month-old wild-type (WT) and PAPP-A knock-out (KO) mice of the same sex and from the same litter (‘womb-mates’) to identify potential mechanisms of skeletal muscle aging and its retardation in PAPP-A deficiency. Top genes regulated in PAPP-A KO compared to WT muscle were associated with increased muscle function, increased metabolism, in particular lipid metabolism, and decreased stress. Fiber cross-sectional area was significantly increased in solei from PAPP-A KO mice. In vitro contractility experiments indicated increased specific force and decreased fatigue in solei from PAPP-A KO mice. Intrinsic mitochondrial oxidative capacity was significantly increased in skeletal muscle of aged PAPP-A KO compared to WT mice. Moreover, 18-month-old PAPP-A KO mice exhibited significantly enhanced endurance running on a treadmill. Thus, PAPP-A deficiency in mice is associated with indices of healthy skeletal muscle function with age.

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Section: Discussionmentioning

confidence: 99%

Comparative gene expression and phenotype analyses of skeletal muscle from aged wild-type and PAPP-A-deficient mice

Conover

Bale

Nair

2016

Experimental Gerontology

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“…In that study, PAPP-A predicted outcomes in TnT-negative patients. Furthermore, differences in stable versus acute CAD may have support in PAPP-A physiology since chronic and transient PAPP-A expression may have differing effects on neointimal formation following vascular injury [42].…”

Section: Discussionmentioning

confidence: 99%

Pregnancy Associated Plasma Protein-A as a Cardiovascular Risk Marker in Patients with Stable Coronary Heart Disease During 10 Years Follow-Up—A CLARICOR Trial Sub-Study

Nilsson

Kastrup

Sajadieh

et al. 2020

JCM

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Elevated pregnancy-associated plasma protein A (PAPP-A) is associated with mortality in acute coronary syndromes. Few studies have assessed PAPP-A in stable coronary artery disease (CAD) and results are conflicting. We assessed the 10-year prognostic relevance of PAPP-A levels in stable CAD. The CLARICOR trial was a randomized controlled clinical trial including outpatients with stable CAD, randomized to clarithromycin versus placebo. The placebo group constituted our discovery cohort (n = 1.996) and the clarithromycin group the replication cohort (n = 1.975). The composite primary outcome was first occurrence of cardiovascular event or death. In the discovery cohort, incidence rates (IR) for the composite outcome were higher in those with elevated PAPP-A (IR 12.72, 95% Confidence Interval (CI) 11.0–14.7 events/100 years) compared to lower PAPP-A (IR 8.78, 8.25–9.34), with comparable results in the replication cohort. Elevated PAPP-A was associated with increased risk of the composite outcome in both cohorts (discovery Hazard Ratio (HR) 1.45, 95% CI 1.24–1.70; replication HR 1.29, 95% CI 1.10–1.52). In models adjusted for established risk factors, these trends were attenuated. Elevated PAPP-A was associated with higher all-cause mortality in both cohorts. We conclude that elevated PAPP-A levels are associated with increased long-term mortality in stable CAD, but do not improve long-term prediction of death or cardiovascular events when added to established predictors.

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“…Moreover, there may be also different effect of acute and chronic increase: chronic PAPP-A (transgene mice) increase was related to accelerated progression of atherosclerotic plaques [41] but was linked to decreased neointimal formation after vascular injury, i.e. insufficient acute increase [42]. Unfortunately, to our knowledge, no data regarding PAPP-A2 dealing with this problem are available to date.…”

Section: Discussionmentioning

confidence: 99%

Pregnancy-Associated Plasma Protein A2 in Hemodialysis Patients: Significance for Prognosis

Kalousová

Dusilová-Sulková

Kubêna

et al. 2017

Kidney Blood Press Res

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Background: Pregnancy-associated plasma protein A (PAPP-A) is associated with adverse outcome of long-term hemodialysis patients (HD). The aim of the study was to test whether its homolog pregnancy-associated plasma protein A2 (PAPP-A2) can be detected in serum of HD patients and to define its significance. Methods: The studied group consisted of 102 long-term HD patients and 25 healthy controls. HD patients were prospectively followed up for five years (2009-2014). PAPP-A2 was measured by surface plasmon resonance biosensor, PAPP-A by time resolved amplified cryptate emission. Results: PAPP-A2, similarly as PAPP-A, was significantly increased in HD patients (median (interquartile range)) PAPP-A2: 6.2 (2.6-10.8) ng/mL, vs. 3.0 (0.7-5.9) ng/mL, p=0.006; PAPP-A: 18.9 (14.3-23.4) mIU/L, vs. 9.5 (8.4-10.5) mIU/L, p<0.001). In HD patients, PAPP-A2 correlated weakly but significantly with PAPP-A (τ=0.193, p=0.004). Unlike PAPP-A, PAPP-A2 was not significant for prognosis of HD patients when tested alone. There was a significant interaction between PAPP-A and PAPP-A2 on the mortality due to infection of HD patients (p=0.008). If PAPP-A was below median, mortality due to infection was significantly higher for patients with PAPP-A2 values above median than for patients with low PAPP-A2 levels (p=0.011). Conclusion: PAPP-A2 is increased in HD patients and interacts with PAPP-A on patients´ prognosis.

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Constitutive expression of pregnancy-associated plasma protein-A in arterial smooth muscle reduces the vascular response to injury in vivo

Abstract: Bale LK, Resch ZT, Harstad SL, Overgaard MT, Conover CA. Constitutive expression of pregnancy-associated plasma protein-A in arterial smooth muscle reduces the vascular response to injury in vivo.

Cited by 11 publications

References 33 publications

Comparative gene expression and phenotype analyses of skeletal muscle from aged wild-type and PAPP-A-deficient mice

Comparative gene expression and phenotype analyses of skeletal muscle from aged wild-type and PAPP-A-deficient mice

Pregnancy Associated Plasma Protein-A as a Cardiovascular Risk Marker in Patients with Stable Coronary Heart Disease During 10 Years Follow-Up—A CLARICOR Trial Sub-Study

Pregnancy-Associated Plasma Protein A2 in Hemodialysis Patients: Significance for Prognosis

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