Placental Pathology and Blood Pressure at Age 7: A Longitudinal Discordant Twin Analysis.

Background: Evidence suggests that the intrauterine environment shapes offspring cardiovascular disease risk. Although placental dysfunction may be an important pathophysiologic pathway, numerous parental and pregnancy characteristics that influence offspring blood pressure are strong confounders of the mechanistic role of the placenta in observational analyses of singletons. Therefore, we leverage twin- and sibling-based comparison designs to determine whether placental pathology is associated with offspring blood pressure at age 7 while mitigating major sources of confounding.

Heterogeneous Cardiac-Derived and Neural Crest-Derived Aortic Smooth Muscle Cells Exhibit Similar Transcriptional Changes After TGFβ Signaling Disruption.

Background: Smooth muscle cells (SMCs) of cardiac and neural crest origin contribute to the developing proximal aorta and are linked to disease propensity in adults.

Methods: We analyzed single-cell transcriptomes of aortic SMCs from adult mice to determine basal states and changes after disrupting TGFβ (transforming growth factor-β) signaling necessary for aortic homeostasis.

Results: A minority of Myh11 lineage-marked SMCs differentially expressed genes suggestive of embryological origin.

Semaglutide Improves Myocardial Perfusion and Performance in a Large Animal Model of Coronary Artery Disease.

Background: Coronary artery disease is the leading cause of death worldwide. It imposes an enormous symptomatic burden on patients, leaving many with residual disease despite optimal procedural therapy and up to one-thirds with debilitating angina amenable neither to procedures, nor to current pharmacological options. Semaglutide (SEM), a GLP-1 (glucagon-like peptide 1) agonist originally approved for management of diabetes, has garnered substantial attention for its capacity to attenuate cardiovascular risk.

Decreased Adipose Lipid Turnover Associates With Cardiometabolic Risk and the Metabolic Syndrome.

Background: Disturbed white adipose tissue function is important for cardiometabolic risk and metabolic syndrome (MetS). Whether this involves adipose lipid turnover (lipolysis and synthesis of triglycerides) is unknown and was presently investigated in subcutaneous adipose tissue, the body's largest fat depot.

Methods: In cross-sectional studies in 78 subjects, adipose lipid age, representing overall lipid turnover (mobilization and storage), and lipid storage capacity were assessed by the incorporation of atmospheric C into adipose lipids.

Extracellular Vesicles From Preeclampsia Disrupt the Blood-Brain Barrier by Reducing CLDN5.

Background: The physiopathology of life-threatening cerebrovascular complications in preeclampsia is unknown. We investigated whether disruption of the blood-brain barrier, generated using circulating small extracellular vesicles (sEVs) from women with preeclampsia or placentae cultured under hypoxic conditions, impairs the expression of tight junction proteins, such as CLDN5 (claudin-5), mediated by VEGF (vascular endothelial growth factor), and activation of KDR (VEGFR2 [VEGF receptor 2]).

Methods: We perform a preclinical mechanistic study using sEVs isolated from plasma of pregnant women with normal pregnancy (sEVs-NP; n=9), sEVs isolated from plasma of women with preeclampsia (sEVs-PE; n=9), or sEVs isolated from placentas cultured in normoxia (sEVs-Nor; n=10) or sEVs isolated from placentas cultured in hypoxia (sEVs-Hyp; n=10).

Sex Differences in Cardiovascular-Kidney-Metabolic Syndrome: 30-Year US Trends and Mortality Risks.

Background: The American Heart Association recently published guidelines on how to clinically identify and categorize individuals with cardiovascular-kidney-metabolic (CKM) syndrome. The extent to which CKM syndrome prevalence and prognosis differ by sex remains unknown. This study aimed to examine the impact of sex on trends in prevalence over 30 years and the long-term prognosis of CKM syndrome in the United States.

Looking Under the Hood at the Cytoskeletal Engine of Platelet Production.

Blood platelets are anucleate cells essential for normal blood hemostasis. To maintain a normal platelet count of 150 000 to 400 000 per μL of blood, 10 platelets must be released each day from precursor cells called megakaryocytes. In this review, we aim to provide an overview of platelet production and evaluate the proposed mechanisms of platelet generation.

DCBLD1 Modulates Angiogenesis by Regulation of the VEGFR-2 Endocytosis in Endothelial Cells.

Background: Unwanted angiogenesis is involved in the progression of various malignant tumors and cardiovascular diseases, and the factors that regulate angiogenesis are potential therapeutic targets. We tested the hypothesis that DCBLD1 (discoidin, CUB, and LCCL domain-containing protein 1) is a coreceptor of VEGFR-2 (vascular endothelial growth factor receptor-2) and modulates angiogenesis in endothelial cells.

Methods: A carotid artery ligation model and retinal angiogenesis assay were used to study angiogenesis using globe knockout or endothelial cell-specific conditional knockout mice in vivo.

SGK1-Mediated Vascular Smooth Muscle Cell Phenotypic Transformation Promotes Thoracic Aortic Dissection Progression.

Background: The occurrence of thoracic aortic dissection (TAD) is closely related to the transformation of vascular smooth muscle cells (VSMCs) from a contractile to a synthetic phenotype. The role of SGK1 (serum- and glucocorticoid-regulated kinase 1) in VSMC phenotypic transformation and TAD occurrence is unclear.

Methods: Four-week-old male Sgk1 ( floxed) and Sgk1;Tagln (smooth muscle cell-specific knockout) mice were administered β-aminopropionitrile monofumarate for 4 weeks to model TAD.

Climate Change and Cardiovascular Disease: Who Is Vulnerable?

Climate change involves a shift in earth's climate indicators over extended periods of time due to human activity. Anthropogenic air pollution has resulted in trapping heat, contributing to global warming, which contributes to worsening air pollution through facilitating oxidizing of air constituents. It is becoming more evident that the effects of climate change, such as air pollution and ambient temperatures, are interconnected with each other and other environmental factors.

Intravital Imaging of Disease Mechanisms in a Mouse Model of CCM Skin Lesions.

Background: Cerebral cavernous malformation (CCM) is a disease characterized by vascular malformations that primarily develop in the brain. These malformations are prone to leak, and their rupture or thrombotic closure can cause life-threatening hemorrhages and strokes. Mouse models have been instrumental to study the disease, but most cause premature lethality, precluding the investigation of disease mechanisms through intravital microscopy.

Andexanet Alfa-Associated Heparin Resistance in Cardiac Surgery: Mechanism and In Vitro Perspectives.

Background: Andexanet alfa (andexanet) is the only Food and Drug Administration-approved antidote for direct FXa (factor Xa) inhibitors but has been reported to cause resistance to unfractionated heparin (UFH). This has delayed anticoagulation for procedures requiring cardiopulmonary bypass. The mechanism, andexanet and UFH dose dependence, and thrombotic risk of andexanet-associated heparin resistance are unknown.