BACKGROUND: Much of what we know about insulin resistance is based on studies from metabolically active tissues such as the liver, adipose tissue, and skeletal muscle. Emerging evidence suggests that the vascular endothelium plays a crucial role in systemic insulin resistance; however, the underlying mechanisms remain incompletely understood. Arf6 (ADP ribosylation factor 6) is a small GTPase that plays a critical role in endothelial cell function. Here, we tested the hypothesis that the deletion of endothelial Arf6 will result in systemic insulin resistance. METHODS: We used mouse models of constitutive endothelial cell–specific Arf6 deletion (Arf6 ^f/− Tie2Cre ⁺ ) and tamoxifen-inducible Arf6 knockout (Arf6 ^f/f Cdh5CreER+). Endothelium-dependent vasodilation was assessed using pressure myography. Metabolic function was assessed using a battery of metabolic assessments including glucose and insulin tolerance tests and hyperinsulinemic-euglycemic clamps. We used a fluorescence microsphere–based technique to measure tissue blood flow. Skeletal muscle capillary density was assessed using intravital microscopy. RESULTS: Endothelial Arf6 deletion impaired insulin-stimulated vasodilation in white adipose tissue and skeletal muscle feed arteries. The impairment in vasodilation was primarily due to attenuated insulin-stimulated nitric oxide bioavailability but independent of altered acetylcholine-mediated or sodium nitroprusside–mediated vasodilation. Endothelial cell–specific deletion of Arf6 also resulted in systematic insulin resistance in normal chow–fed mice and glucose intolerance in high-fat diet–fed obese mice. The underlying mechanisms of glucose intolerance were reductions in insulin-stimulated blood flow and glucose uptake in the skeletal muscle and were independent of changes in capillary density or vascular permeability. CONCLUSIONS: Results from this study support the conclusion that endothelial Arf6 signaling is essential for maintaining insulin sensitivity. Reduced expression of endothelial Arf6 impairs insulin-mediated vasodilation and results in systemic insulin resistance. These results have therapeutic implications for diseases that are associated with endothelial cell dysfunction and insulin resistance such as diabetes.

Doxorubicin (DOXO) is a widely used chemotherapy drug that can damage blood vessels and promote cardiovascular disease. This study shows that MitoQ, a mitochondria-targeted antioxidant, protects endothelial cells from DOXO-induced oxidative stress, DNA damage, and senescence. By preserving mitochondrial health, MitoQ may prevent vascular toxicity in cancer patients receiving DOXO, offering a potential strategy to improve cardiovascular outcomes in survivorship.

During the COVID-19 pandemic, the high prevalence of comorbidities and the disparities between the public and private health subsystems in Mexico substantially contributed to the severe impact of the disease. The objective of this study was to evaluate and compare the risk factors at admission for in-hospital mortality of patients with COVID-19. A 2-year retrospective cohort study of hospitalized adult patients with COVID-19 pneumonia was conducted at a private tertiary care center. The study population consisted of 1258 patients with a median age of 56 ± 16.5 years, of whom 1093 recovered (86.8%) and 165 died (13.1%). In the univariate analysis, older age (p < 0.001), comorbidities such as hypertension (p < 0.001) and diabetes (p < 0.001), signs and symptoms of respiratory distress, and markers of acute inflammatory response were significantly more frequent in non-survivors. The multivariate analysis showed that older age (p < 0.001), the presence of cyanosis (p = 0.005), and previous myocardial infarction (p = 0.032) were independent predictors of mortality. In the studied cohort, the risk factors present at admission associated with increased mortality were older age, cyanosis, and a previous myocardial infarction, which can be used as valuable predictors for patients’ outcomes. To our knowledge, this is the first study analyzing predictors of mortality in COVID-19 patients attended in a private tertiary hospital in Mexico.

Aging reshapes the vascular endothelium in unexpected ways. Using lineage tracing in mice, we show that endothelial cells undergo age-dependent clonal expansion, particularly in atheroprone regions exposed to disturbed blood flow. This process is amplified by DNA damage and reflects the selective expansion of preexisting clones rather than increased recruitment. Endothelial clonal expansion may represent an underrecognized mechanism driving vascular remodeling during aging and genotoxic stress.

During the COVID-19 pandemic, the high prevalence of comorbidities in Mexico, as well as the disparities between public and private health subsystems, substantially contributed to the severe impact it had in the country. The objective of this study was to evaluate and compare risk factors present at admission for mortality of hospitalized patients with COVID-19. A 2-year retrospective cohort study of hospitalized adult patients with COVID-19 was conducted at a private tertiary care center. The study population consisted of 1,258 patients with a median age of 56 ± 16.5 years, of whom 1,093 recovered (86.8%) and 165 died (13.1%). In the univariate analysis, older age (p <0.001), comorbidities such as hypertension (p <0.001) and diabetes (p <0.001), signs and symptoms of respiratory distress, and markers of acute inflammatory response were significantly more frequent in non-survivors. The multivariate analysis showed that older age (p <0.001), the presence of cyanosis (p 0.005) and previous myocardial infarction (p 0.032) were independent predictors for mortality. In the studied cohort, risk factors present at admission associated with an increased risk of death were older age, cyanosis and a previous myocardial infarction, which can be used as valuable predictors for patients’ outcomes. To our knowledge, this is the first study analyzing predictors of mortality in COVID-19 patients attended on a private tertiary hospital in Mexico.