Shiming Liu

Cardiovascular diseases (CVDs) are a leading cause of death but are largely preventable. Consequently, devising effective predictive models to identify hig

Abdominal aortic calcification (AAC) and atherosclerosis are prevalent conditions among older adults, and recent research suggests that their association may extend beyond the effects of aging alone. An essential instrument for determining the possibility of cardiovascular disease (CVD) is the cardiometabolic index (CMI), a new lipid-based index sensitive to visceral obesity. However, little has been established about the relationship between CMI and AAC. We examined CMI and AAC data from the National Health and Nutrition Examination Survey (NHANES) conducted in 2013–2014 for this study. The relationship between AAC, severe abdominal aortic calcification (SAAC), and CMI was assessed using multiple linear and logistic regression models. The overall trend was visualized using smoothed curve modeling. Subgroup analyses were conducted to find possible moderating factors. Among the 2704 participants included, those with higher CMI levels exhibited much greater AAC scores and a higher prevalence of SAAC. In model 3, elevated CMI positively correlated with AAC (0.25 (0.09, 0.41)) and with the odds of SAAC (OR = 1.35 (1.09, 1.67)). Participants in the highest CMI quartile had an AAC score that was 0.65 units higher (β = 0.65 (0.26, 1.04)) and an 114% higher risk of SAAC (OR = 2.14 (1.29, 3.54)). Subgroup analyses indicated sex and smoking status significantly modified the relationship between CMI, AAC, and SAAC, while previously diagnosed with congestive heart failure (CHF) and heart attack significantly moderated the association between CMI and AAC. These results imply that greater AAC scores and a higher risk of SAAC are linked to heightened CMI, which represents visceral fat storage and disturbed lipid metabolism. Our findings indicate that CMI is correlated with AAC in certain demographic and cardiovascular subgroups, suggesting its potential as an exploratory indicator of elevated AAC risk in these populations.

[This corrects the article DOI: 10.7150/thno.22788.].

Background: Several long non-coding RNAs (lncRNAs) have been associated with cell senescence, termed senescence-associated lncRNAs (SAL-RNAs). However, the mechanisms involved for SAL-RNAs in aging are not fully elucidated. In the present study, we investigated the effects of SAL-RNAs on aged human bone marrow-derived mesenchymal stem cells (hBM-MSCs), and the possible means to counteract such effects to improve the regenerative capacity of aged hBM-MSCs. Methods: By comparing the lncRNAs expression of hBM-MSCs derived from young and old individuals, lnc-CYP7A1-1 was identified as being significantly increased with age. Using predictive software, the expression of Spectrin Repeat Containing Nuclear Envelope Protein 1 (SYNE1), was found to be decreased with age. Next, through lentiviral constructs, we downregulated the expression of lnc-CYP7A1-1 or SYNE1 in hBM-MSCs separately. Additionally, hBM-MSCs proliferation, survival, migration, and senescence were investigated in vitro. In vivo, lnc-CYP7A1-1 downregulated aged hBM-MSCs were implanted into infarcted mouse hearts after myocardial infarction (MI), and cardiac function was measured. Through lentivirus-mediated downregulation of lnc-CYP7A1-1 in aged hBM-MSCs, we revealed that cell senescence was decreased, whereas cell proliferation, migration, and survival were increased. On the other hand, downregulation of SYNE1, the target gene of lnc-CYP7A1-1, in young hBM-MSCs increased cell senescence, yet decreased cell proliferation, migration, and survival. Downregulation of lnc-CYP7A1-1 in aged hBM-MSCs induced cell rejuvenation, yet this effect was attenuated by repression of SYNE1. In vivo, transplantation of lnc-CYP7A1-1 downregulated old hBM-MSCs improved cardiac function after MI. Conclusion: Down-regulation of lnc-CYP7A1-1 rejuvenated aged hBM-MSCs and improved cardiac function when implanted into the infarcted mouse hearts, possibly through its target gene SYNE1.

Reduced quantity and quality of stem cells in aged individuals hinders cardiac repair and regeneration after injury. We used young bone marrow (BM) stem cell antigen 1 (Sca‐1) cells to reconstitute aged BM and rejuvenate the aged heart, and examined the underlying molecular mechanisms. BM Sca‐1⁺ or Sca‐1⁻ cells from young (2–3 months) or aged (18–19 months) GFP transgenic mice were transplanted into lethally irradiated aged mice to generate 4 groups of chimeras: young Sca‐1⁺, young Sca‐1⁻, old Sca‐1⁺, and old Sca‐1⁻. Four months later, expression of rejuvenation‐related genes (Bmi1, Cbx8, PNUTS, Sirt1, Sirt2, Sirt6) and proteins (CDK2, CDK4) was increased along with telomerase activity and telomerase‐related protein (DNA‐PKcs, TRF‐2) expression, whereas expression of senescence‐related genes (p16^INK4a, P19^ARF, p27^Kip1) and proteins (p16^INK4a, p27^Kip1) was decreased in Sca‐1⁺ chimeric hearts, especially in the young group. Host cardiac endothelial cells (GFP⁻CD31⁺) but not cardiomyocytes were the primary cell type rejuvenated by young Sca‐1⁺ cells as shown by improved proliferation, migration, and tubular formation abilities. C‐X‐C chemokine CXCL12 was the factor most highly expressed in homed donor BM (GFP⁺) cells isolated from young Sca‐1⁺ chimeric hearts. Protein expression of Cxcr4, phospho‐Akt, and phospho‐FoxO3a in endothelial cells derived from the aged chimeric heart was increased, especially in the young Sca‐1⁺ group. Reconstitution of aged BM with young Sca‐1⁺ cells resulted in effective homing of functional stem cells in the aged heart. These young, regenerative stem cells promoted aged heart rejuvenation through activation of the Cxcl12/Cxcr4 pathway of cardiac endothelial cells.

Background: To improve the regenerative capacity of aged individuals, we reconstituted bone marrow (BM) of aged mice with young Sca-1 cells, which repopulated cardiac progenitors and prevented cardiac dysfunction after a myocardial infarction (MI). However, the mechanisms involved were incompletely elucidated. This study aimed to investigate whether young, highly regenerative BM Sca-1 cells exert their cardio-protective effects on the aged heart through reactivation of the epithelial-to-mesenchymal transition (EMT) process.