Ferrara Elisabetta, D'Albenzio Alessandro, Bassignani Jessica, Di Tanna Isabella, Murmura Giovanna, Balice Giuseppe
Department of Human Sciences, Law, and Economics, Telematic University "Leonardo Da Vinci"-UNIDAV, Torrevecchia Teatina, 66100 Chieti, Italy.
Complex Operative Unit of Pathological Addiction, Addiction Service, ASL2 Abruzzo, 66100 Chieti, Italy.
Int J Mol Sci. 2025 Aug 9;26(16):7710. doi: 10.3390/ijms26167710.
The relationship between periodontitis and cardiovascular diseases (CVDs) extends beyond epidemiological associations, as demonstrated by meta-analyses showing a significantly increased risk for coronary heart disease development. At the core of this association lies systemic inflammation, where periodontal pathogens initiate cascades of pro-inflammatory cytokines. This inflammatory response manifests through substantial elevations in interleukin-1 beta (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in periodontitis patients. Oxidative stress plays a crucial role, with Nicotinamide Adenine Dinucleotide Phosphate (NADPH) Oxidase 2 (NOX2) activation leading to markedly increased superoxide production compared to healthy controls. The peroxynitrite formed via NO-superoxide interaction accumulates in affected vascular tissues, substantially reducing nitric oxide (NO) bioavailability. Molecular mimicry mechanisms are evidenced by heat shock protein sharing significant sequence homology with human HSP60, triggering autoimmune responses that affect cardiovascular tissues. Epigenetic modifications show specific alterations, with Nrf2 target gene expression substantially downregulated in chronic periodontal inflammation, particularly affecting heme oxygenase-1 (HO-1) and NAD(P)H:Quinone Oxidoreductase 1 (NQO1) expression. These molecular pathways create a complex network of interactions that fundamentally link periodontal and cardiovascular pathologies.
牙周炎与心血管疾病（CVDs）之间的关系超出了流行病学关联，荟萃分析表明牙周炎会显著增加冠心病发病风险，这一点就证明了这一点。这种关联的核心在于全身炎症，牙周病原体引发促炎细胞因子级联反应。这种炎症反应表现为牙周炎患者体内白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）大幅升高。氧化应激起着关键作用，与健康对照相比，烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶2（NOX2）激活导致超氧化物生成显著增加。一氧化氮与超氧化物相互作用形成的过氧亚硝酸盐在受影响血管组织中蓄积，大幅降低一氧化氮（NO）生物利用度。热休克蛋白与人类HSP60具有显著序列同源性，引发影响心血管组织的自身免疫反应，从而证明了分子模拟机制。表观遗传修饰呈现特定改变，在慢性牙周炎症中，Nrf2靶基因表达大幅下调，尤其影响血红素加氧酶-1（HO-1）和NAD（P）H：醌氧化还原酶1（NQO1）表达。这些分子途径形成了一个复杂的相互作用网络，从根本上把牙周病和心血管病联系起来。
