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Hepatocyte growth factor in patients with coronary artery disease and its relation to periodontal condition
Division of Clinical Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden. (PEAS Institute, Linköping, Sweden)
Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet.
Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet.
Linköpings universitet, Institutionen för medicin och hälsa, Klinisk fysiologi. Linköpings universitet, Hälsouniversitetet.
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2012 (Engelska)Ingår i: Results in Immunology, E-ISSN 2211-2839, Vol. 2, s. 7-12Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Hepatocyte growth factor (HGF) is an angiogenic, cardioprotective factor important for tissue and vascular repair. High levels of HGF are associated with chronic inflammatory diseases, such as coronary artery disease (CAD) and periodontitis, and are suggested as a marker of the ongoing atherosclerotic event in patients with CAD. Periodontal disease is more prevalent among patients with CAD than among healthy people. Recent studies indicate a reduced biological activity of HGF in different chronic inflammatory conditions. Biologically active HGF has high affinity to heparan sulfate proteoglycan (HSPG) on cell-membrane and extracellular matrix. The aim of the study was to investigate the serum concentration and the biological activity of HGF with ELISA and surface plasmon resonance (SPR), respectively, before and at various time points after percutaneous coronary intervention (PCI) in patients with CAD, and to examine the relationship with periodontal condition. The periodontal status of the CAD patients was examined, and the presence of P. gingivalis in periodontal pockets was analyzed with PCR. The HGF concentration was significantly higher, at all time-points, in patients with CAD compared to the age-matched controls (P< 0.001), but was independent of periodontal status. The HGF concentration and the affinity to HSPG adversely fluctuated over time, and the biological activity increased one month after intervention in patients without periodontitis. We conclude that elevated concentration of HGF but with reduced biological activity might indicate a chronic inflammatory profile in patients with CAD and periodontitis.

Ort, förlag, år, upplaga, sidor
Elsevier, 2012. Vol. 2, s. 7-12
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
URN: urn:nbn:se:liu:diva-86207DOI: 10.1016/j.rinim.2011.12.002OAI: oai:DiVA.org:liu-86207DiVA, id: diva2:575714
Tillgänglig från: 2012-12-11 Skapad: 2012-12-11 Senast uppdaterad: 2024-01-18
Ingår i avhandling
1. Periodontitis and coronary artery disease: Studies on the association between periodontitis and coronary artery disease
Öppna denna publikation i ny flik eller fönster >>Periodontitis and coronary artery disease: Studies on the association between periodontitis and coronary artery disease
2012 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Periodontitis and coronary artery disease (CAD) are highly prevalent in Sweden’s population; both diseases have complicated pathogeneses and clinical manifestations due to immune-system triggered inflammation. Research in recent years reported that inflammation is a significant active participant in many chronic diseases. The literature described a CAD-periodontitis association, but underlying mechanisms are not fully understood. It is important to acquire knowledge about how periodontitis might influence CAD, which is one of the major causes of illness and death in western countries. Because periodontitis can be treated, this knowledge, when complemented with more knowledge about the CAD-periodontitis association, could lead to CAD prevention.

The overall aim of studies reported in this thesis were to investigate the CAD-periodontitis association, and specifically, to: (i) compare periodontal conditions in patients with CAD and subjects without a history of CAD; (ii) study whether or not periodontal status influences outcomes in known CAD over an 8-year period; (iii) study whether or not concentrations and biological activity of hepatocyte growth factor (HGF) in serum from patients with severe CAD are different – depending on whether or not the subjects had periodontitis; and (iv) study concentrations and biological activity of hepatocyte growth factor in serum, saliva, and gingival crevicular fluid in healthy subjects with or without periodontitis. Here is a brief summary:

In study I, 161 patients with CAD and 162 controls were compared regarding periodontal disease prevalence and severity. CAD patients had significant coronary stenosis and underwent percutaneous coronary intervention (PCI) or coronary artery by-pass grafts (CABG). Healthy controls were recruited from Sweden’s population database. Twenty-five per cent of the CAD patients had severe periodontitis, compared to 8% of the controls. In a multiple logistic regression analysis (controlled for age and smoking), severe periodontitis indicated an odds ratio of 5.74 (2.07–15.90) for CAD.

Study II: Periodontal status was re-examined in 126 CAD patients and 121 controls from the initial sample after 8 years. Periodontal status at baseline was analysed and related to CAD endpoints (i.e., myocardial infarction, new PCI or CABG or death due to CAD) recorded from patients’ medical records and from the death index maintained by the National Board of Health and Welfare. The difference in periodontitis prevalence and severity between the two groups remained unchanged during the 8-year follow up. No significant differences were found regarding CAD endpoints during follow-up in relation to baseline periodontal status in the CAD-patient group.

In study III, higher HGF serum concentrations (p<0.001) were found in CAD patients, compared to healthy blood donors, which reflects chronic inflammation. In CAD patients without periodontitis, HGF concentrations increased significantly 24 hours after PCI – in parallel with increased HGF biological activity. In CAD patients with periodontitis, only small fluctuations were seen in HGF values, i.e., concentration and biological activity. HGF biological activity was temporarily elevated after PCI but only in patients without periodontitis. Thus chronic inflammation related to periodontitis might reduce HGF biological activity.

In study IV, HGF concentration and biological activity in saliva, in gingival crevicular fluid (GCF), and serum were compared between 30 generally healthy subjects with severe untreated periodontitis and 30 healthy subjects without periodontitis. Compared to periodontally healthy controls, periodontal patients showed higher HGF concentrations in saliva p<0.001, gingival crevicular fluid p<0.0001, and in serum p<0.001. HGF biological activity (measured as the binding affinity to its HSPG and c-MET receptors) was significantly reduced in saliva (p<0.0001) and GCF samples (p<0.0001 for HSPG and p<0.01 for c-MET) from periodontitis patients. The only significant difference in serum samples was an increases in c-MET binding three minutes after subgingival debridement in periodontitis patients (p<0.05), which might reflect that patients had active bursts of periodontitis.

In conclusion, CAD patients more often showed severe periodontitis but there were no differences in CAD endpoints during the eight-year follow-up in relation to baseline periodontal status. Periodontitis seems to influence HGF concentration and biological activity in CAD patients, but studies on factors that cause lower HGF biological activity are necessary – to find out if periodontal treatment influences HGF biological activity. Healthy periodontitis patients had higher HGF concentrations locally and systemically, but biological activity was reduced. This might indicate that periodontitis can influence wound healing and tissue repair in other body parts.

Ort, förlag, år, upplaga, sidor
Linköping: Linköping University Electronic Press, 2012. s. 84
Serie
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1343
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
urn:nbn:se:liu:diva-86213 (URN)978-91-7519-748-7 (ISBN)
Disputation
2013-02-01, Berzeliussalen, Campus US, Linköpings universitet, Linköping, 13:00 (Svenska)
Opponent
Handledare
Anmärkning

The ISBN 987‐91‐7519‐748‐7 is incorrect. Correct ISBN is 978‐91‐7519‐748‐7.

Tillgänglig från: 2012-12-11 Skapad: 2012-12-11 Senast uppdaterad: 2019-12-10Bibliografiskt granskad

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