Elevated Platelet-Derived Growth Factor AB/BB is Associated with a Lower Risk of Recurrent Vascular Events in Stroke Patients

Abstract

Background

Platelet-derived growth factor (PDGF)-AB and BB have been shown to possess angiogenic properties in vivo, and decreased levels have been linked to plaque instability in atherosclerosis. Little work has been done to determine if PDGF is associated with outcomes after stroke, in particular cognitive outcomes. Therefore, in this sudy, we investigated the association between PDGFand both vascular and cognitive outcomes in a cohort of patients with recent nondisabling ischemic stroke.

Methods

Three hundred nine patients recruited within six-months of a transient ischemic attack or nondisabling ischemic stroke [modified Rankin Scale (mRS) ⩽ 3] were followed for up to five-years. Cox proportional-hazard regression analyses were performed to investigate the association of PDGF levels with the risk of death, recurrent vascular events, dependency, and incident dementia, while logistic regression analyses were performed to investigate the association of PDGF levels with the risk of significant cognitive decline. Significant cognitive decline was defined as: (a) a decline of cognitive status from no cognitive impairment or mild cognitive impairment with no dementia to moderate cognitive impairment with no dementia or (b) conversion to dementia.

Results

Patients (mean age 60 years) were mostly male (64%) and of Chinese ethnicity (85%) and had posterior circulation or lacunar infarcts (73%). In univariate analysis, PDGF was significantly associated with a lower risk of recurrent vascular events [hazard ratio (HR) 0·61; 95% confidence interval (CI) 0·44–0·84]. In multivariate analysis adjusting for treatment, PDGF was independently associated with a lower risk of recurrent vascular events (HR 0·62; 95% CI 0·46–0·85). PDGF levels were not associated with the risk of the other outcomes of interest.

Conclusions

Higher levels of PDGF-AB/BB were independently associated with a lower risk of recurrent vascular events in a cohort of convalescent nondisabled stroke patients. Our findings suggest that PDGF-AB/BB may potentially serve as a prognostic marker for outcomes pos- stroke and, if this result is validated in larger samples, a potential therapeutic target.

Keywords

growth factors outcomes prognosis

Get full access to this article

View all access options for this article.

References

Stiles

Capone

Scher

Antoniades

Van Wyk

Pledger

. Dual control of cell growth by somatomedins and platelet-derived growth factor. Proc Natl Acad Sci U S A 1979; 76:1279–83.

Iihara

Sasahara

Hashimoto

Uemura

Kikuchi

Hazama

. Ischemia induces the expression of the platelet-derived growth factor-B chain in neurons and brain macrophages in vivo. J Cereb Blood Flow Metab 1994; 14:818–24.

Niimi

. Cerebral angiogenesis induced by growth factors: intravital microscopic studies using models. Clin Hemorheol Microcirc 2003; 29:149–56.

Krupinski

Issa

Bujny

. A putative role for platelet-derived growth factor in angiogenesis and neuroprotection after ischemic stroke in humans. Stroke 1997; 28:564–73.

Navarro-Sobrino

Rosell

Hernandez-Guillamon

. A large screening of angiogenesis biomarkers and their association with neurological outcome after ischemic stroke. Atherosclerosis 2011; 216:205–11.

Chowdhury

Ghosh

Slevin

Smyth

Alexander

Serracino-Inglott

. A comparative study of carotid atherosclerotic plaque microvessel density and angiogenic growth factor expression in symptomatic versus asymptomatic patients. Eur J Vasc Endovasc Surg 2010; 39:388–95.

Nguyen

Nakamura

Hori

. Cognitive and socio-emotional deficits in platelet-derived growth factor receptor-beta gene knockout mice. PLoS ONE 2011; 6:e18004.

De Schryver

; European/Australian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT) group. Design of ESPRIT: an international randomized trial for secondary prevention after non-disabling cerebral ischaemia of arterial origin. Cerebrovasc Dis 2000; 10:147–50.

Bonita

Beaglehole

. Recovery of motor function after stroke. Stroke 1988; 19:1497–500.

10.

Mead

Lewis

Wardlaw

Dennis

Warlow

. How well does the Oxfordshire community stroke project classification predict the site and size of the infarct on brain imaging? J Neurol Neurosurg Psychiatry 2000; 68:558–62.

11.

Folstein

McHugh

. ‘Mini-Mental State’. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12:189–98.

12.

Narasimhalu

Ang

De Silva

. Severity of CIND and MCI predict incidence of dementia in an ischemic stroke cohort. Neurology 2009; 73:1866–72.

13.

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th edn. Arlington, VA, American Psychiatric Association, 2000.

14.

Graham

Rockwood

Beattie

. Prevalence and severity of cognitive impairment with and without dementia in an elderly population. Lancet 1997; 349:1793–6.

15.

Slevin

Kumar

Gaffney

Kumar

Krupinski

. Can angiogenesis be exploited to improve stroke outcome? Mechanisms and therapeutic potential. Clin Sci (Lond) 2006; 111:171–83.

16.

Vincent

Rafii

. Vascular frontiers without borders: multifaceted roles of platelet-derived growth factor (PDGF) in supporting postnatal angiogenesis and lymphangiogenesis. Cancer Cell 2004; 6:307–9.

17.

Yamagishi

Imaizumi

. Pericyte biology and diseases. Int J Tissue React 2005; 27:125–35.