A groundbreaking study on myocardial infarction shows infections!

[AribertDeckers]

29.8.2025
A groundbreaking study on myocardial infarction shows infections!


https://x.com/vipintukur/status/1961132063358370247

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Vipin M. Vashishtha @vipintukur

A pioneering study has demonstrated for the first time that myocardial infarction may be an infectious disease. This discovery challenges the conventional understanding of the pathogenesis of myocardial infarction and opens new avenues for treatment, diagnostics, and even vaccine development. 1/
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8:21 PM · Aug 28, 2025
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Vipin M. Vashishtha @vipintukur

According to the study, an infection may trigger myocardial infarction. Using a range of advanced methodologies, the research found that, in coronary artery disease, atherosclerotic plaques containing cholesterol may harbor a gelatinous, asymptomatic biofilm formed by bacteria over years or even decades. Dormant bacteria within the biofilm remain shielded from both the patient's immune system and antibiotics because they cannot penetrate the biofilm matrix.  2/
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Vipin M. Vashishtha @vipintukur

Of the bacteria detected, oral viridans group streptococcal DNA was the most common, being found in 42.1% of coronary plaques and 42.9% of endarterectomies. Immunopositivity for viridans streptococci correlated with severe atherosclerosis (P<0.0001) in both series and death from coronary heart disease (P=0.021) or myocardial infarction (P=0.042).  3/
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Vipin M. Vashishtha @vipintukur

Among the viridans streptococcal strains, TLR2 was the most activated bacterial‐signaling pathway. Genome‐wide expression analysis of endarterectomy samples showed upregulation of bacterial recognition pathways.  4/
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Vipin M. Vashishtha @vipintukur

What Question Should Be Addressed Next?

➡️ Could a short‐term antibiotics treatment given at the acute phase affect the outcome of myocardial infarction, and would it be possible to develop new diagnostic imaging and prevention methods for bacterial biofilm?  5/5

https://www.ahajournals.org/doi/10.1161/JAHA.125.041521
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[AribertDeckers]

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Research Article
Originally Published 6 August 2025
Open Access

Viridans Streptococcal Biofilm Evades Immune Detection and Contributes to Inflammation and Rupture of Atherosclerotic Plaques

Pekka J. Karhunen, MD, PhD https://orcid.org/0000-0002-0320-571X pekka.j.karhunen@tuni.fi,
Tanja Pessi, PhD,
Sohvi Hörkkö, MD, PhD https://orcid.org/0000-0003-2118-5270,
Vesa Karhunen, DDS,
Sirkka Goebeler, MD, PhD https://orcid.org/0000-0002-8968-8328,
Anne‐Mari Louhelainen, MD https://orcid.org/0000-0002-9696-3877,
Mika Martiskainen, MD,
Teppo Haapaniemi, MSc,
Johanna Lappeteläinen, MSc,
Tommi Ijäs, MSc,
Leo‐Pekka Lyytikäinen, MD,
Emma Raitoharju, PhD https://orcid.org/0000-0002-7023-8706,
Thanos Sioris, MD, PhD,
Sari Tuomisto, PhD https://orcid.org/0000-0002-2376-6338,
Heini Huhtala, MSc https://orcid.org/0000-0003-1372-430X,
Chunguang Wang, MD, PhD https://orcid.org/0000-0001-5569-321X,
Claudia Monaco, MD, PhD https://orcid.org/0000-0003-1985-4914,
Niku Oksala, MD, PhD, DSc (med) https://orcid.org/0000-0001-5336-3719,
Terho Lehtimäki, MD, DDS, PhD https://orcid.org/0000-0002-2555-4427, and
Reijo Laaksonen, MD, PhD

Author Info & Affiliations
Journal of the American Heart Association
Volume 14, Number 16
https://doi.org/10.1161/JAHA.125.041521

Abstract

Background

Bacterial DNA from the oral cavity, respiratory tract, gut, and skin has been detected in atherosclerotic plaques, suggesting a role in chronic inflammation linked to atherosclerosis. Chronic bacterial infections often form biofilms resistant to antibiotics and immune detection, giving rise to a new generation of virulent bacteria in suitable conditions. This study explores the role of the immune system in bacterial‐induced inflammation of atherosclerotic plaques.

Methods

Coronary plaques from 121 sudden death victims and endarterectomy samples from 96 surgical patients were analyzed using bacterial real‐time quantitative polymerase chain reaction, immunohistochemistry, and genome‐wide expression analysis. TLR (toll‐like receptor) signaling was examined in bacterial‐activated TLR cell lines.

Results

Of the bacteria detected, oral viridans group streptococcal DNA was the most common, being found in 42.1% of coronary plaques and 42.9% of endarterectomies. Immunopositivity for viridans streptococci correlated with severe atherosclerosis (P<0.0001) in both series and death from coronary heart disease (P=0.021) or myocardial infarction (P=0.042). Viridans streptococci colonized the core of the atheroma as a biofilm unrecognized by macrophages of the innate immune system. In contrast, immunopositive streptococci that appeared to have originated from the biofilm infiltrated the ruptured fibrous cap of the atheroma in endarterectomy samples and coronary plaques and were detected by pattern‐recognizing receptors and coexpressed with the adaptive immune response. Among the viridans streptococcal strains, TLR2 was the most activated bacterial‐signaling pathway. Genome‐wide expression analysis of endarterectomy samples showed upregulation of bacterial recognition pathways.

Conclusions

Latent chronic bacterial inflammation evades immune detection and may contribute to the pathogenesis of complicated atherosclerotic plaques and fatal myocardial infarction.


Nonstandard Abbreviations and Acronyms

ATCC
    American Type Culture Collection
GWE
    genome‐wide expression analysis
MyD88
    myeloid differentiation primary response protein
NF‐kB
    nuclear factor kappa‐light‐chain‐enhancer of activated B cells
TLR
    toll‐like receptor
TSDS
    Tampere Sudden Death Study
TVS
    Tampere Vascular Study

Research Perspective

What Is New?
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Coronary plaques and clinical endarterectomy samples harbored DNA from several oral bacteria among which oral viridans streptococci were the most common, being found in phagocytes and as a biofilm inside atherosclerotic plaques as examined by bacterial immunohistochemistry.
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Viridans streptococcal biofilm was not detected by macrophages of the innate immune system, which, in contrast, detected virulent streptococci that were dispersed from the biofilm infiltrating the ruptured fibrous cap of the atheroma of people experiencing sudden cardiac death, also causing activation of the adaptive immune system in support of the infection hypothesis of myocardial infarction.

What Question Should Be Addressed Next?
•
Could a short‐term antibiotics treatment given at the acute phase affect the outcome of myocardial infarction, and would it be possible to develop new diagnostic imaging and prevention methods for bacterial biofilm?

The present view on the pathogenesis of atherosclerosis entails that it is a chronic subclinical inflammation driven by oxidized low‐density lipoprotein (oxLDL) cholesterol. Inflammation is key in both the initial development of the lipid‐containing atheroma and its transformation into a vulnerable rupture‐prone coronary atheroma.1, 2, 3, 4 Experimental evidence suggests that an important step in the inflammation inside a coronary atheroma is the generation of immune response against oxLDL and its main epitope, phosphocholine.5, 6 OxLDL is recognized by the innate immune system, using germline‐encoded pattern recognition receptors, including TLRs (toll‐like receptors).7 Interestingly, although being the major epitope of oxLDL, phosphocholine is also found on a variety of bacteria, such as Streptococcus pneumoniae, in which phosphocholine is a prominent constituent of the lipoteichoic acid components of the cell‐wall polysaccharide.8, 9 Although TLR2 and TLR4 with their coreceptor CD14 were originally detected as key components of the pathogen‐associated molecular machinery that recognizes gram‐positive and gram‐negative bacteria, they also identify a wide variety of endogenous structures, including oxLDL.10, 11 TLR signaling initiates cytokine production by activating transcription factor NF‐kB (nuclear factor‐kappa B) through its adaptor protein MyD88 (myeloid differentiation primary response protein).12 Thus, the immune responses that have evolved to combat bacterial infections are shared with those involved in the immune response to the endogenous inflammatory components of atherogenesis.2
The possibility that infectious agents are involved in the chronic inflammation of coronary plaques has been considered for a long time.3, 13 Reports from the late 1980s on the association of Chlamydia antibodies and chronic dental infections with myocardial infarction (MI)14, 15 greatly increased the academic interest in the infection hypothesis that was subsequently tested in large long‐term antibiotics trials. Most of these trials failed, as orally administered bactericidal antibiotics effective against Chlamydia pneumoniae16, 17, 18 and periodontal bacteria19 yielded no reduction in the rate of secondary cardiovascular events.20 Contrasting results in smaller trials were also published.20, 21, 22, 23 Currently, it is known that chronic inflammation is often due to a bacterial biofilm that can evade the innate immune system and is resistant to antibiotics, which possibly may explain the trial failures. A dormant biofilm may be activated by some poorly known factors, executing the production of a new generation of virulent bacteria that break out of the biofilm.24, 25, 26
Using broad‐range 16‐S rDNA polymerase chain reaction (PCR), followed by cloning and sequencing, we found in 2005 that coronary atheromas collected at autopsy contained DNA of viridans group streptococci, among other species of bacteria commonly found in the oral cavity.27 Viridans group streptococcal DNA was also detected in most thrombus aspirates from patients with MI,28 in ruptured cerebral aneurysms,29 in thrombus aspirates from surgical patients with lower‐limb arterial and deep venous thrombosis,30 and in cerebral thrombi from patients with acute ischemic stroke treated with thrombectomy31; in the last‐mentioned series, the presence of viridans streptococci was also confirmed by bacterial immunohistochemistry.32 The presence of DNA from viridans streptococci has also been confirmed by other studies.33, 34, 35 The recent approach of using 16S rRNA gene sequencing–based metagenomic studies has revealed that atherosclerotic plaques harbor DNA sequences from dozens or even hundreds of oral, intestinal, skin or environmental bacteria35, 36, suggesting the presence of a microbiome. However, these sequences are mostly present in tiny <1% fractions, the majority of them most probably carried by single or small groups of phagocytes or being contaminants from PCR reagents and other laboratory equipment or environmental elements, with no clinical significance.37
Viridans streptococci are harmless commensals in the oral cavity, where they act as initial colonizers in the development of a dental biofilm38 known as dental plaque. However, they have been found to be the major species of bacteria detected in blood following tooth extraction and other dental procedures39, 40, 41 and are considered to be among the most common pathogenetic agents of infective endocarditis,42, 43 which is a typical example of a chronic bacterial infection due to a bacterial biofilm.44
The overriding question is the issue of causality—do the bacteria that can be found in atherosclerotic plaques have any causal role in the development of the plaques, or are they or their DNA present as a consequence of inflammation? Sensitive molecular probes may detect bacterial DNA engulfed by phagocytic cells also originating from a noncardiac site, such as the gingiva, skin, respiratory tract, or intestinal tract.45 Bacteria might attach as a biofilm onto the uneven surface of the plaques following transient bacteremia with no pathogenic significance. In a real infection, the pathogen invasion activates the innate immune system and there should be evidence of the presence of the agent in an atherosclerotic plaque but not in normal blood vessels.13 In an autopsy study, this idea may be carried further by studying whether the presence of bacteria in a coronary atheroma is linked with the rupture and thrombosis of the atheroma and with death due to an MI. In this setting, the absence of bacteria should associate with a normal artery or nonruptured atheroma and with a noncoronary cause of death.
In the present study, we aimed to investigate the role of oral bacteria, and particularly that of viridans streptococci, and the innate immune system in the inflammation of atherosclerotic plaques, in addition to examining their role as a risk factor for a fatal MI. This was achieved by first analyzing the presence and prevalence of oral bacterial DNA in atheromas with real‐time quantitative PCR (RT‐qPCR) and by applying bacterial immunohistochemistry in a unique series of people experiencing sudden out‐of‐hospital death. We then used bacterial‐stimulated TLR cell lines to study in vitro which TLR signaling routes the streptococci and other candidate bacteria preferred to activate. Next, we analyzed immunohistochemically whether receptors of TLR signaling pathways were coexpressed with bacterial immunopositivity in ruptured fibrous caps of coronary atheromas and whether the adaptive immune system was also activated. To confirm the results of our studies on autopsy cases, we also studied the presence of oral bacterial genomes and bacterial immunopositivity in a series of atherosclerotic endarterectomy samples from surgical patients. With these patient samples, we performed a genome‐wide expression (GWE) analysis of atherosclerotic plaques to study the up‐ or downregulation of genes in TLR‐dependent signaling pathways for recognizing bacteria.

METHODS

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Tampere Sudden Death Study

The TSDS (Tampere Sudden Death Study) comprises a prospective series of ...

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The full text of the study:
https://www.ahajournals.org/doi/10.1161/JAHA.125.041521