Aortic dissection (AD) is a life‐threatening medical emergency characterized by adverse vascular remodeling. Coiled‐coil domain‐containing protein 80 (CCDC80) plays an essential role in regulating cardiovascular remodeling. This study aims to define the role of CCDC80 in the formation and development of AD. Significant downregulation of CCDC80 in vascular smooth muscle cell (VSMC) in human and mouse AD is identified. Then, CCDC80 knockout mice (CCDC80 ^−/− ) and VSMC‐specific CCDC80 knockout mice (CCDC80 ^fl/fl SM22α Cre ⁺ ) treated with angiotensin II (Ang II) or Ang II combined with β‐aminopropionitrile monofumarate (BAPN) frequently develop AD with higher frequency and severity, accompanied by severe elastin fragmentation and collagen deposition. Mechanistically, CCDC80 interacts with JAK2, and CCDC80 deficiency promotes VSMC phenotype switching, proliferation, and migration as well as matrix metalloproteinase production by activating the JAK2/STAT3 signaling pathway. Moreover, the JAK2/STAT3 pathway‐specific inhibitor ameliorates adverse vascular remodeling and reduces AD formation in CCDC80‐knockout mice by mitigating VSMC phenotype switching. In conclusion, CCDC80 deficiency exacerbates the progression of events leading to AD by activating the JAK2/STAT3 pathway involved in regulating the phenotype switching and function of VSMCs. These findings highlight that CCDC80 is a potential key target for the prevention and treatment of AD.

Background: Previous intracoronary imaging studies have shown that coronary artery calcium (CAC) is an independent risk factor of stent underexpansion; however, limited preintervention assessments of CAC have been performed using noninvasive methods. We aimed to determine the association between lesion-specific CAC score and stent underexpansion.Methods: In this retrospective observational study, we included 416 lesions from 359 patients who underwent intravascular ultrasound (IVUS)-guided stent implantation. CAC of each lesion was quantified using the Agatston method derived from either nongated noncontrast chest CT (NCCT) or electrocardiogram-gated coronary CT angiography (CCTA). The primary endpoint was stent underexpansion defined as minimum stent area of <80% of the average reference lumen area.Results: Overall, stent underexpansion occurred in 144 (34.6%) of 416 lesions. Lesion-specific CAC score was significantly negatively correlated with the stent expansion rate (in NCCT cohort, r = 0.8113, P < 0.05; in CCTA cohort, r = 0.8024, P < 0.05). The optimal cutoff values of lesion-specific CAC score to predict stent underexpansion were >200 in both NCCT (sensitivity, 91.4%; specificity, 66.8%) and CCTA (sensitivity, 84.6%; specificity, 64.3%) cohort, which were associated with 24.94-fold increased risk of stent underexpansion in NCCT cohort and 13.56-fold increased risk of stent underexpansion in CCTA cohort.Conclusions: In this study, we found that lesion-specific CAC scores in both NCCT and CCTA cohorts were significantly independently associated with an increased risk of stent underexpansion, and the cutoff value to predict stent underexpansion was >200.

Septic cardiomyopathy (SC) is a sepsis-mediated cardiovascular complication characterized by cardiac dysfunction. Emerging evidence indicated that exercise training confers protection against SC; however, the underlying mechanisms are not yet fully understood. In this study, we identified a novel exercise-derived peptide, apolipoprotein A1 peptide (named ApoA1tide), through mouse plasma peptidomic screening. Subsequent experiments revealed that ApoA1tide mitigated lipopolysaccharide (LPS)-induced SC in murine models, as evidenced by enhanced cardiac function, prolonged survival, and improved myocardial structure. Moreover, ApoA1tide was found to inhibit inflammatory responses, cardiomyocyte apoptosis, and oxidative stress in mice subjected to LPS induction. Correspondingly, in vitro experiments demonstrated that ApoA1tide suppressed LPS-induced apoptosis and oxidative stress in neonatal rat cardiac myocytes (NRCMs). Additionally, ApoA1tide enhanced autophagic activity in both LPS-induced mice and NRCMs. Mechanistically, RNA sequencing identified CCAAT/enhancer-binding protein β (C/EBPβ) as the primary target of ApoA1tide. The expression of C/EBPβ was upregulated following ApoA1tide treatment. Overexpression of C/EBPβ in NRCMs resulted in increased expression of autophagy-related genes, including LC3B, Atg3, Atg4b, and Atg7. Conversely, Knockdown of C/EBPβ eliminated the enhancement of autophagy induced by ApoA1tide, along with the protective effects of ApoA1tide on cardiac functionality, cardiomyocyte apoptosis, oxidative stress, and inflammation. These findings indicate that ApoA1tide exerts its protective effects against SC by enhancing C/EBPβ-mediated autophagy. Our study provides a novel therapeutic strategy for SC. Graphical abstract Schematic representation of the effects of ApoA1tide on sepsis-induced cardiac dysfunction. ApoA1tide, a peptide derived from exercise, attenuates LPS-induced SC. This protective effect is mediated through C/EBPβ-regulated autophagy. Specifically, ApoA1tide promotes autophagy by upregulating C/EBPβ expression, which subsequently increases the expression of autophagy-related genes such as LC3B, Atg3, Atg4b, and Atg7. The enhancement of autophagy suppresses inflammatory responses, cardiomyocyte apoptosis, and oxidative stress in mice exposed to LPS, thereby ameliorating cardiac dysfunction.