Microcephalic osteodysplastic primordial dwarfism type II (MOPDII) is caused by biallelic loss-of-function variants in pericentrin ( PCNT ), and premature coronary artery disease (CAD) is a complication of the syndrome. Histopathology of coronary arteries from patients with MOPDII who died of CAD in their 20s showed extensive atherosclerosis. Hyperlipidemic mice with smooth muscle cell–specific (SMC-specific) Pcnt deficiency ( Pcnt ^SMC–/– ) exhibited significantly greater atherosclerotic plaque burden compared with similarly treated littermate controls despite similar serum lipid levels. Loss of PCNT in SMCs induced activation of heat shock factor 1 (HSF1) and consequently upregulated the expression and activity of HMG-CoA reductase (HMGCR), the rate-limiting enzyme in cholesterol biosynthesis. The increased cholesterol biosynthesis in Pcnt ^SMC–/– SMCs augmented PERK signaling and phenotypic modulation compared with control SMCs. Treatment with the HMGCR inhibitor, pravastatin, blocked the augmented SMC modulation and reduced plaque burden in hyperlipidemic Pcnt ^SMC–/– mice to that of control mice. These data support the notion that Pcnt deficiency activates cellular stress to increase SMC modulation and plaque burden, and targeting this pathway with statins in patients with MOPDII has the potential to reduce CAD in these individuals. The molecular mechanism uncovered further emphasizes SMC cytosolic stress and HSF1 activation as a pathway driving atherosclerotic plaque formation independently of cholesterol levels.

Atherosclerosis remains a major driver for cardiovascular disease (CVD), despite advancements in traditional risk factor management therapies. Recent evidence emphasizes the crucial role of the gut microbiome in the progression of atherosclerosis and plaque rupture, highlighting a promising therapeutic avenue. This review focuses on the intertwined relationship between the gut microbiome, its metabolites, and atherosclerosis and CVD, also highlighting the potential therapeutic role of probiotics and prebiotics. Given the diverse and unique gut microbiota signatures among individuals, a one-size-fits-all therapeutic approach is unlikely to be effective. Personalized treatment strategies are therefore necessary. Here, we discussed how Artificial Intelligence (AI) can be leveraged to analyze individual gut microbiome profiles from microbiome sequencing, predict treatment response, and optimize therapeutic strategies based on individual patients, which would significantly improve outcomes of the treatment for atherosclerosis patients.

Atherosclerosis remains a major driver for cardiovascular disease (CVD), despite advancements in traditional risk factor management therapies. Recent evidence emphasizes the crucial role of the gut microbiome in the progression of atherosclerosis and plaque rupture, highlighting a promising therapeutic avenue. This review focuses on the intertwined relationship between the gut microbiome, its metabolites, and atherosclerosis and CVD, also highlighting the potential therapeutic role of probiotics and prebiotics. Given the diverse and unique gut microbiota signatures among individuals, a one-size-fits-all therapeutic approach is unlikely to be effective. Personalized treatment strategies are therefore necessary. Here we discussed how Artificial Intelligence (AI) can be leveraged to analyze individual gut microbiome profiles from microbiome sequencing, predict treatment response, and optimize therapeutic strategies based on individual patients which would significantly improve outcomes of the treatment for atherosclerosis/CVD patients.

This descriptive review synthesizes mechanistic and clinical evidence on the periodontal disease (PD)–atherosclerotic cardiovascular disease (ASCVD) axis to clarify how oral inflammation, bacterial translocation, immune dysregulation, and oxidative stress may influence vascular pathology and to identify where causal inference and interventional evidence remain insufficient. We searched PubMed, Web of Science, ScienceDirect, and Google Scholar for studies on microbial translocation, systemic inflammation, endothelial dysfunction, and interventional outcomes. Evidence supports a robust epidemiological association between PD and ASCVD; proposed mechanisms prominently involve Porphyromonas gingivalis-driven immune modulation and endothelial injury. Periodontal therapy consistently reduces inflammatory biomarkers and improves surrogate vascular measures, while effects on hard cardiovascular outcomes are suggestive but not definitive. Recognizing PD as a modifiable oral inflammatory condition may refine cardiovascular risk assessment and motivate integrated prevention, while future work should prioritize well-designed randomized trials with standardized PD/ASCVD phenotyping.