Ali Farmanieh
1 
, Afsoon Jalali Ara
2 , Sara Rashki Ghalehno
3 , Parsa Malek
4 , Mitra Rostami
5 , Seyed Sasan Amiri
1 , Negar Khaneshi
6 , Reza Faramarzzadeh
7 , Golara Abdolmohammadi
8 , Maryam Onsori
9* 1 Department of Medicine and Surgery, University of Napoli Federico II, Napoli, Italy
2 Department of Oral and Maxillofacial Radiology, Dental School, Islamic Azad University of Medical Sciences, Tehran, Iran
3 Department of Cardiology, School of Medicine, Amir al Momenin Hospital, Zabol University of Medical Sciences, Zabol, Iran
4 School of Dentistry, Manila Centro Escalar University, Philippines
5 School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran
6 School of Dentistry, Hamedan University of Medical Sciences, Hamedan, Iran
7 Department of Cardiology, Seyed-al-shohada Cardiology Hospital, Urmia University of Medical Science, Urmia, Iran
8 Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Iran
9 Department of Operative Dentistry, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
Abstract
A growing body of evidence implicates dysbiosis of the oral microbiome as a significant, modifiable risk factor for cardiovascular disease. This dysbiosis, often manifesting as periodontitis, initiates local inflammation and tissue destruction, however its systemic consequences are profound. Key mechanisms linking oral dysbiosis to cardiovascular disease involve the induction of endothelial dysfunction and chronic systemic inflammation. Pathogens and their virulence factors enter the bloodstream through inflamed periodontal tissues, directly impairing endothelial nitric oxide production and bioavailability, promoting vasoconstriction, leukocyte adhesion, and a pro-thrombotic state. Concurrently, microbial components activate innate immune receptors on endothelial and immune cells, triggering sustained release of pro-inflammatory cytokines and acute-phase proteins. The low-grade, systemic inflammation accelerates atherosclerosis by promoting foam cell formation, plaque instability, and vascular remodeling. Epidemiological studies consistently associate periodontitis with increased risks of myocardial infarction, stroke, and atherosclerosis severity, independent of traditional risk factors.