Mots-C
Mitochondrial open reading frame of the 12S rRNA-c, MT-RNR1, Mitochondrial-derived peptide MOTS-c
β-Amyloid and mitochondrial-derived peptide-c are additive predictors of adverse outcome to high-on-treatment platelet reactivity in type 2 diabetics with revascularized coronary artery disease.
Ikonomidis. Ignatios I; Katogiannis. Konstantinos K; Kyriakou. Elias E; Taichert. Maria M; Katsimaglis. Georgios G; Tsoumani. Maria M; Andreadou. Ioanna I; Maratou. Eirini E; Lambadiari. Vaia V; Kousathana. Foteini F; Papadopoulou. Anna A; Varlamos. Charalampos C; Plotas. Panagiotis P; Parissis. John J; Stamatelopoulos. Kimon K; Alexopoulos. Dimitrios D; Dimitriadis. George G; Tsantes. Argirios E AE
Key Findings
- High platelet reactivity plus beta‑amyloid >51 pg/mL gave about a 4‑fold higher risk of major cardiac events.
- Low MOTS‑c (<167 ng/mL) also gave about a 4‑fold higher risk when combined with high platelet reactivity.
- The combined risk prediction held true in an independent validation cohort of diabetic heart patients.
Practical Outcomes
- If you can measure platelet reactivity, beta‑amyloid, or MOTS‑c, you could identify a higher‑risk state and focus on interventions that lower platelet stickiness (e.g., ensure clopidogrel effectiveness) and boost mitochondrial health (e.g., regular exercise, NAD+ precursors). While routine testing isn’t common, the data suggest that improving mitochondrial function and reducing amyloid load may be worth exploring as part of a broader longevity strategy.
Summary
In people with type‑2 diabetes and heart disease, having overly sticky platelets (high on‑clopidogrel platelet reactivity) together with either high blood beta‑amyloid or low levels of the mitochondrial peptide MOTS‑c sharply raises the chance of a heart attack or death over two years. The study shows these three factors add up to predict risk, and the finding was confirmed in another group of patients.
Abstract
Increased β-amyloid and decreased mitochondrial-derived peptide (MOTS-c), are reported in diabetes. We investigated their additive value to high on-clopidogrel platelet reactivity (HPR) for adverse outcome in type 2 diabetics after recent revascularization. In 121 type II diabetics, treated with clopidogrel and aspirin, (93 males, mean age 67.2 years) we measured: (a) maximum platelet aggregation to adenosine diphosphate (ADP) by light transmission aggregometry (LTAmax), (b) malondialdehyde (MDA), as oxidative stress marker, (c) MOTS-c, (d) β-amyloid blood levels. Cardiac death and acute coronary syndromes (MACE) were recorded during 2 years of follow-up. Out of 121 patients, 32 showed HPR (LTAmax > 48%,). At baseline, HPR was associated with β-amyloid > 51 pg/ml (p = 0.006) after adjusting clinical variables, HbA1c, MOTS-c, MDA and medication. During follow-up, 22 patients suffered a MACE. HPR, β-amyloid > 51 pg/ml and MOTS-c < 167 ng/ml were predictors of MACE (relative risk 3.1, 3.5 and 3.8 respectively, p < 0.05) after adjusting for confounders and medication. There was significant interaction between HPR and β-amyloid or MOTS-c for the prediction of MACE (p < 0.05). Patients with HPR and β-amyloid > 51 mg/dl or HPR and MOTS-c concentration < 167 ng/ml had a fourfold higher risk for MACE than patients without these predictors (relative risk 4.694 and 4.447 respectively p < 0.01). The above results were confirmed in an external validation cohort of 90 patients with diabetes and CAD. Increased β-amyloid or low MOTS-c are additive predictors to high on-clopidogrel platelet reactivity for adverse outcome in diabetics with CAD during 2-years follow-up. Clinical Trial Registration-URL: https://www.clinicaltrials.gov. Unique identifier: NCT04027712.
Study Information
pubmed
2020
2020-02-12T00:00:00.000Z
10.1007/s11239-020-02060-4
13
31