Cardiovascular diseases are chronic inflammatory diseases that affect a large segment of society. Coronary heart disease (CHD), the most common cardiovascular disease, progresses over several years and affects millions of people worldwide. Chronic infections may contribute to the systemic inflammation and enhance the risk for CHD. Periodontitis is one of the most common chronic infections that affects up to 50% of the adult population. Under inflammatory conditions the activation of endogenous degradation pathways mediated by immune responses leads to the release of destructive cellular molecules from both resident and immigrant cells. Matrix metalloproteinases (MMPs) and their regulators can activate each other and play an important role in immune response via degrading extracellular matrix components and modulating cytokines and chemokines. The action of MMPs is required for immigrant cell recruitment at the site of inflammation. Stimulated neutrophils represent the major pathogen-fighting immune cells that upregulate expression of several proteinases and oxidative enzymes, which can degrade extracellular matrix components (e.g. MMP-8, MMP-9 and neutrophil elastase). The activity of MMPs is regulated by endogenous inhibitors and/or candidate MMPs (e.g. MMP-7). The balance between MMPs and their inhibitors is thought to mirror the proteolytic burden. Thus, neutrophil-derived biomarkers, including myeloperoxidase, may activate proteolytic destructive cascades that are involved in subsequent immune-pathological events associated with both periodontitis and CHD. Here, we review the existing studies on the contribution of MMPs and their regulators to the infection-related pathology. Also, we discuss the possible proteolytic involvement and role of neutrophil-derived enzymes as an etiological link between chronic periodontitis and CHD.

An association exists between chronic infection‐induced inflammation, such as periodontitis, and acute coronary syndrome (ACS). We studied the association of serum neutrophil markers, myeloperoxidase (MPO), matrix metalloproteinase (MMP)‐8, tissue inhibitor of metalloproteinase (TIMP)‐1 concentrations and MMP‐8/TIMP‐1 ratio, with the risk of recurrent ACS. Radiographic periodontal status was recorded from 141 patients with acute non‐Q‐wave infarction or unstable angina pectoris, who participated in a double‐blind, placebo‐controlled study with clarithromycin for 3 months. Serum samples were collected within arrival to the hospital, at 1 week, 3 months and 1 year. Recurrent ACS events were registered during the 1‐year follow‐up. In the whole population, high serum MPO concentrations at 1 week (fourth quartile versus quartiles 1–3) were associated with the risk of recurrent ACS with a relative risk (RR) of 2.52 (95% CI, 1.277–4.980; P = 0.008). In patients without periodontal disease, high MPO concentration at 1 week and 1 year predicted recurrent ACS with RRs of 3.54 (1.600–7.831; P = 0.002) and 2.87 (1.171–7.038; P = 0.021), respectively. In the placebo group, but not in the clarithromycin group, high serum MMP‐8/TIMP‐1 ratio at 1 week predicted recurrent ACS with an RR of 3.23 (1.295–8.063; P = 0.012). Our results suggest that high serum neutrophil markers reflect increased risk of recurrent ACS, especially in patients without periodontal disease and not receiving antimicrobial medication.

Owing to molecular mimicry, periodontal pathogen carriage may result in a systemic cross‐reactive immune response with the host. The analyses were performed to investigate if serum antibody levels to human heat shock protein 60 (HSP60) are associated with the antibody levels and salivary carriage of two periodontal pathogens, Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis, as well as with the dental status in patients with acute coronary syndrome (ACS). ACS patients (n = 141) were monitored at baseline when entering to hospital, and after 1 week, 3 months and 1 year. Periodontal status was recorded by dental radiographs, and A. actinomycetemcomitans and P. gingivalis were detected by PCR from saliva at baseline. Serum IgG and IgA antibody levels were determined at all time points. All antibody levels remained quite stable during the follow‐up. Serum IgG‐class antibody levels to A. actinomycetemcomitans and HSP60 had a strong positive correlation with each other at all time points (r∼0.4, P < 0.05). Mean serum IgG antibody levels to HSP60 were significantly higher in the A. actinomycetemcomitans IgG‐ and IgA‐seropositive than in the seronegative patients, but did not differ between the pathogen carriers compared to the non‐carriers. HSP60 antibody levels did not differ significantly between the edentulous, non‐periodontitis and periodontitis patients. Despite the observed cross‐reactivity in the systemic IgG‐class antibody response to HSP60 and A. actinomycetemcomitans, the pathogen carriage in saliva or the periodontal status did not affect the HSP60 antibody levels in ACS patients.

Doxycycline decreases the systemic inflammatory burden in patients with myocardial infarction and especially down-regulates MMP-7, MMP-8, and MMP-8/TIMP-1. Doxycycline might prevent or reduce the risk of secondary myocardial infarctions by providing a systemic anti-proteolytic and -inflammatory shield.

No abstract