Dormant biofilms of oral viridans streptococci within arterial plaques may drive inflammation and rupture, linking poor oral health to fatal cardiovascular events.
Highlights:
- Oral bacteria viridans streptococci were found in over 60 percent of arterial plaques
- Biofilm-forming bacteria in plaque cores may evade immune response and trigger rupture
- Poor dental health may be linked to fatal heart conditions through bacterial circulation
Bacterial DNA from common oral, respiratory, gut, and skin microbes has been detected in arterial plaques, suggesting that persistent inflammation could be central to the development of atherosclerosis (1✔ ✔Trusted Source
Viridans Streptococcal Biofilm Evades Immune Detection and Contributes to Inflammation and Rupture of Atherosclerotic Plaques
).
A recent publication in the Journal of the American Heart Association examines how chronic inflammation in plaques, triggered by bacteria and the immune system’s reaction to them, might contribute to atherosclerosis.
Atherosclerosis involves ongoing low-level inflammation initiated by the oxidation of low-density lipoprotein, or LDL, which becomes deposited within the inner lining of coronary arteries. This accumulation, along with its growth and eventual rupture, is fueled by inflammation.
Immune System Overlap Between LDL and Bacterial Components
Studies indicate that the innate immune system identifies oxidized LDL using pattern recognition receptors such as toll-like receptors. Phosphocholine, a key part of oxidized LDL, is also present in many bacterial species, including Streptococcus pneumoniae.
The immune responses to bacterial infections and to inflammation-driving molecules in plaques show notable similarities. For example, Toll-like receptors 2 and 4 are critical in identifying many pathogens, but also bind to host elements like oxidized LDL, thereby initiating inflammatory signaling.
Revival of the Infection Hypothesis in Arterial Disease
This overlap leads to speculation that plaque formation might involve infection. Roughly five decades ago, scientists proposed this idea based on associations between heart disease and infections like Chlamydia and poor oral health. Yet, while early findings were hopeful, larger trials using antibiotics largely failed to prevent cardiovascular events.
An alternative view suggested that bacteria forming biofilms may cause chronic inflammation without triggering a typical immune response. These biofilms could shield bacteria from antibiotics and immune cells. Under certain conditions, dormant biofilms may become active, allowing bacteria to invade and infect arterial plaques.
Tracing Bacteria in Heart and Vascular Tissues
This theory prompted the current investigation, whose authors previously identified viridans streptococci in blood clots and blocked vessels of patients with heart attacks, strokes, and deep vein thrombosis.
Viridans streptococci are usually harmless and reside in the mouth, helping form dental plaque. These bacteria frequently enter the bloodstream during dental work and are commonly seen in infective endocarditis. However, their presence in arterial plaques could either be a sign of inflammation or merely due to random attachment during circulation. If random, they would likely not be confined to plaques alone.
Circulation and Hypoxia Enable Bacterial Invasion
In normal arteries, the immune system uses complement factors to tag bacteria for removal by macrophages. However, when plaques grow and oxygen levels fall, new blood vessels sprout within the plaque, potentially delivering bacteria straight from the blood into the plaque itself. These microbes can enter the bloodstream after dental treatments, and poor oral hygiene has been linked to sudden cardiac deaths.
Researchers analyzed coronary plaques from 121 individuals who died suddenly in Finland as part of the Tampere Sudden Death Study, along with plaque samples from 96 patients who underwent endarterectomy procedures. They used techniques including real-time quantitative polymerase chain reaction, immunohistochemistry, and genome-wide expression analysis to identify bacteria and immune activation pathways.
Association with Severe Coronary Conditions
Bacteria were found in 65 percent of plaques from sudden death cases and 58 percent of surgical specimens. In both sets, the most prevalent species was oral viridans streptococcus, appearing in 42 percent of coronary plaques and 43 percent of endarterectomy samples.
Using targeted antibodies, the researchers confirmed the presence of viridans streptococci antigens in the plaques, 60 percent of sudden death samples and 53 percent of surgical ones, supporting the notion that these bacteria were present, not just mistaken for oxidized LDL. The authors suggest these bacteria could be involved early in plaque development.
The presence of viridans streptococcus correlated with advanced atherosclerosis and deaths caused by coronary artery disease.
Biofilm Formation Vs Dispersed Bacteria
Significantly, viridans streptococci formed biofilms deep in the core and walls of the plaques. These biofilms protected them from immune detection. In contrast, scattered bacteria at plaque rupture sites activated both innate and adaptive immune systems. Biofilms are typical in long-term infections and are made of substances that conceal bacterial surfaces from immune cells.
At the rupture points, scattered bacteria were identified by toll-like receptor pathways. These receptors can stimulate inflammatory molecules and enzymes like matrix metalloproteinases that degrade the plaque’s fibrous cap, a key step in forming clots that cause heart attacks or strokes.
Severity of Plaque Tied to Bacterial Presence
More advanced plaques were more likely to test positive for viridans streptococci. Only 11 percent of arteries with minimal plaque showed bacterial presence. However, 100 percent of ruptured plaques in sudden death cases and 75 percent in surgical cases contained these bacteria.
As the authors state, “this evidence suggests that viridans streptococci are not innocent bystanders in the plaque.”
Immune Activation and Genetic Analysis
The toll-like receptor 2 pathway was the most consistently activated signaling route in these samples. Immune responses were present at the plaque sites, and gene expression data showed heightened activity in pathways linked to bacterial detection in the surgical specimens.
The authors conclude that the shift from a stable coronary plaque to one likely to rupture may be influenced by a persistent bacterial infection hidden within a biofilm. Similarly, symptomatic peripheral artery disease might be associated with such infections.
These findings reinforce the role of inflammation in recurring heart problems, as seen in earlier trials like the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study. New diagnostic or treatment approaches might include targeting bacterial components of plaque inflammation.
Future work could examine whether a brief course of antibiotics during a heart attack might prevent dangerous bacterial activity within plaques.
To sum up, the role of oral bacteria, particularly viridans streptococci, in accelerating and destabilizing atherosclerotic plaques is vital. Their ability to form biofilms and evade immune responses suggests a new dimension in cardiovascular disease management, linking oral health more closely than ever to heart health. Further investigation could open new paths for prevention and treatment.
Reference:
- Viridans Streptococcal Biofilm Evades Immune Detection and Contributes to Inflammation and Rupture of Atherosclerotic Plaques – (https://www.ahajournals.org/doi/10.1161/JAHA.125.041521)
Source-Medindia
