Journal: Frontiers in Physiology

Article Title: Transcriptomic profiling of the sex-linked biological pathways of severe pulmonary arterial hypertension associated with endothelial cell caveolin-1 depletion and chronic hypoxia

doi: 10.3389/fphys.2026.1794886

Figure Lengend Snippet: Effect of Caveolin-1 (Cav1) knockout and reconstitution on mouse survival in hypoxia. Representative Western Blots against CAV1 in (A) male (n = 3 – 9) and (B) female (n=4-7) mice after 6 weeks of hypoxia. All western blot images used for quantification are available as Source Data. Data is quantified relative to whole protein using ponceau staining. Post-hoc 2-way analysis of variance (ANOVA) with Bonferonni’s multiple comparisons test where *P-value < 0.05, ****P-value < 0.0001. Data presented as mean ± standard error of the mean (SEM). (C) Survival curves of wildtype (n=30), Caveolin-1-knockout (n=37), and reconstituted mice (n=12) in hypoxia (10% oxygen) over 60 days. (D) Survival curve comparing male (n=16) and female Caveolin-1 (n=21) knockout over 60 days of hypoxia. Post-hoc survival curve analysis was performed with Mantel-Cox comparisons.

Article Snippet: Cav1 -/- (Cav1 tm1Mls /J) and B6/129SJ2 wild-type control mice were originally purchased from Jackson Labs. Cav1-RC mice ( ) were obtained from William Sessa, Yale University.

Techniques: Knock-Out, Western Blot, Staining

Journal: Frontiers in Physiology

Article Title: Transcriptomic profiling of the sex-linked biological pathways of severe pulmonary arterial hypertension associated with endothelial cell caveolin-1 depletion and chronic hypoxia

doi: 10.3389/fphys.2026.1794886

Figure Lengend Snippet: Right ventricular (RV) function and structure of Caveolin-1 (Cav1) global knockout or Caveolin-1 endothelial-specific reconstituted male and female mice exposed to 6 weeks of hypoxia. Control (Con), Cav1 global knockout (KO), and Caveolin-1 endothelial-specific reconstituted (RC) are plotted by normoxia (Normoxia), white bars, or hypoxia (Hypo), dotted bars. (A) Right ventricular systolic pressure (RVSP) (n = 4 – 16) (B) Right ventricular free wall thickness (RVFWT) (n = 4 – 11) (C) Right Ventricular Hypertrophy (RVH) as determined by the weight ratio of the right ventricle divided by the sum of left ventricle and septum (RV/(LV+S)) (n = 4 – 25) (D) Pulmonary acceleration time (PAT) (n = 4 – 15) (E) Tricuspid annular plane systolic excursion (TAPSE) (n = 4 – 15). Post-hoc 3-way ANOVA analysis with Bonferonni’s multiple comparisons tests where *P-value < 0.05, **P-value < 0.01, ***P-value <0.001, ****P-value < 0.0001. Data presented as mean ± standard error of the mean (SEM).

Article Snippet: Cav1 -/- (Cav1 tm1Mls /J) and B6/129SJ2 wild-type control mice were originally purchased from Jackson Labs. Cav1-RC mice ( ) were obtained from William Sessa, Yale University.

Techniques: Knock-Out, Control

Journal: Frontiers in Physiology

Article Title: Transcriptomic profiling of the sex-linked biological pathways of severe pulmonary arterial hypertension associated with endothelial cell caveolin-1 depletion and chronic hypoxia

doi: 10.3389/fphys.2026.1794886

Figure Lengend Snippet: Cardiac echocardiography of Caveolin-1 (Cav1) global knockout or Caveolin-1 endothelial-specific reconstituted male and female mice exposed to 6 weeks of hypoxia. Control (Con), Cav1 global knockout (KO), and Caveolin-1 endothelial-specific reconstituted (RC) are plotted by normoxia (Normoxia), white bars, or hypoxia (Hypo), dotted bars. (A) Cardiac Output (CO) (n = 4 – 15) (B) Ejection Fraction (EF) (n = 4 – 15) C) Fractional Shortening (FS) (n = 4 – 15) (D) Stroke Volume (SV) (n = 4 – 15) (E) Isovolumetric relaxation time (IVRT) (n = 4 – 25). Post-hoc 3-way ANOVA analysis with Bonferonni’s multiple comparisons test where *P-value < 0.05, **P-value < 0.01, ***P-value < 0.001, ****P-value < 0.0001. Data presented as mean ± standard error of the mean (SEM).

Article Snippet: Cav1 -/- (Cav1 tm1Mls /J) and B6/129SJ2 wild-type control mice were originally purchased from Jackson Labs. Cav1-RC mice ( ) were obtained from William Sessa, Yale University.

Techniques: Knock-Out, Control

Journal: Frontiers in Physiology

Article Title: Transcriptomic profiling of the sex-linked biological pathways of severe pulmonary arterial hypertension associated with endothelial cell caveolin-1 depletion and chronic hypoxia

doi: 10.3389/fphys.2026.1794886

Figure Lengend Snippet: Blood gas measurements of Caveolin-1 (Cav1) global knockout or Caveolin-1 endothelial-specific reconstituted male and female mice exposed to 6 weeks of hypoxia. Control (Con), Cav1 global knockout (KO), and Caveolin-1 endothelial-specific reconstituted (RC) are plotted by normoxia (Normoxia, white bars), or hypoxia (Hypo, dotted bars). (A) Oxygen saturation (sO2) (n = 3 – 8) (B) Partial pressure of oxygen (pO2) (n = 4 – 7) (C) Partial pressure of carbon dioxide (pCO2) (n = 3 – 8) (D) pH levels (pH) (n = 4 – 8) (E) Extracellular base excess (BeCef) (n = 3 – 8) (F) Bicarbonate (HCO3) (n = 3 – 8) (G) Lactate (n = 3 – 7) (H) Hemoglobin (Hgb) (n = 5 – 9) (I) Hemocrit (Hct) (n = 5 – 9). Post-hoc 3-way ANOVA analysis with Bonferonni’s multiple comparisons test where *P-value < 0.05, **P-value < 0.01, ****P-value < 0.0001. Data presented as mean ± standard error of the mean SEM).

Article Snippet: Cav1 -/- (Cav1 tm1Mls /J) and B6/129SJ2 wild-type control mice were originally purchased from Jackson Labs. Cav1-RC mice ( ) were obtained from William Sessa, Yale University.

Techniques: Knock-Out, Control

Journal: Frontiers in Physiology

Article Title: Transcriptomic profiling of the sex-linked biological pathways of severe pulmonary arterial hypertension associated with endothelial cell caveolin-1 depletion and chronic hypoxia

doi: 10.3389/fphys.2026.1794886

Figure Lengend Snippet: Pairwise comparison of differentially expressed genes between Caveolin-1 knockout (Cav1-KO) and wildtype control (Control) mouse lungs in normoxic conditions. Male (control n=3, Cav1-KO n=3) and female (control n=3, Cav1-KO n=2) comparisons were performed separately. The top 50 differentially expressed genes (DEG) upregulated and downregulated are shown in descending order of significance based on adjusted P-value (P adj ) for (A) female and (B) male lungs. DEG thresholds were set at Log2Foldchange > 1, P adj <0.05. Z-score coloring represents relative gene expression across all groups. Samples are sorted by complete hierarchical clustering. Gene Ontology (GO) analysis for (C) Female and (D) Male samples are shown as the top 20 gene ontologies in descending order of P adj . The X-axis represents the number of DEGs in this comparison that underlies the significant GO.

Article Snippet: Cav1 -/- (Cav1 tm1Mls /J) and B6/129SJ2 wild-type control mice were originally purchased from Jackson Labs. Cav1-RC mice ( ) were obtained from William Sessa, Yale University.

Techniques: Comparison, Knock-Out, Control, Gene Expression

Journal: Frontiers in Physiology

Article Title: Transcriptomic profiling of the sex-linked biological pathways of severe pulmonary arterial hypertension associated with endothelial cell caveolin-1 depletion and chronic hypoxia

doi: 10.3389/fphys.2026.1794886

Figure Lengend Snippet: Pairwise comparison of differentially expressed genes between Caveolin-1 knockout (Cav1-KO) and wildtype control (Control) mouse lungs in hypoxic conditions. Male and female comparisons were performed separately (n=3 in each group). The top 50 differentially expressed genes (DEG) upregulated and downregulated are shown in descending order of significance based on adjusted P-value (P adj ) for (A) female and (B) male lungs. DEG thresholds were set at Log2Foldchange > 1, P adj <0.05. Z-score coloring represents relative gene expression across all groups. Samples are sorted by complete hierarchical clustering. Gene Ontology (GO) analysis for (C) Female and (D) Male samples are shown as the top 20 gene ontologies in descending order of P adj . The X-axis represents the number of DEGs in this comparison that underlies the significant GO.

Article Snippet: Cav1 -/- (Cav1 tm1Mls /J) and B6/129SJ2 wild-type control mice were originally purchased from Jackson Labs. Cav1-RC mice ( ) were obtained from William Sessa, Yale University.

Techniques: Comparison, Knock-Out, Control, Gene Expression

Journal: Frontiers in Physiology

Article Title: Transcriptomic profiling of the sex-linked biological pathways of severe pulmonary arterial hypertension associated with endothelial cell caveolin-1 depletion and chronic hypoxia

doi: 10.3389/fphys.2026.1794886

Figure Lengend Snippet: Pairwise comparison of differentially expressed genes between endothelial Caveolin-1 reconsituted (Cav1-RC) and Caveolin-1 knockout (Cav1-KO) mouse lungs in normoxic conditions. Male (Cav1-KO n=3, Cav1-RC n=3) and female (Cav1-KO n=2, Cav1-RC n=3) comparisons were performed separately. The top 50 differentially expressed genes (DEG) upregulated and downregulated are shown in descending order of significance based on adjusted P-value (P adj ) for (A) female and (B) male lungs. DEG thresholds were set at Log2Foldchange > 1, P adj <0.05. Z-score coloring represents relative gene expression across all groups. Samples are sorted by complete hierarchical clustering. Gene Ontology (GO) analysis for (C) Female and (D) Male samples are shown as the top 20 gene ontologies in descending order of P adj . The X-axis represents the number of DEGs in this comparison that underlies the significant GO.

Article Snippet: Cav1 -/- (Cav1 tm1Mls /J) and B6/129SJ2 wild-type control mice were originally purchased from Jackson Labs. Cav1-RC mice ( ) were obtained from William Sessa, Yale University.

Techniques: Comparison, Knock-Out, Gene Expression

Journal: Frontiers in Physiology

Article Title: Transcriptomic profiling of the sex-linked biological pathways of severe pulmonary arterial hypertension associated with endothelial cell caveolin-1 depletion and chronic hypoxia

doi: 10.3389/fphys.2026.1794886

Figure Lengend Snippet: Pairwise comparison of differentially expressed genes endothelial Caveolin-1 reconsituted (Cav1-RC) and Caveolin-1 knockout (Cav1-KO) mouse lungs in hypoxic conditions. Male and female comparisons were performed separately (n=3 for each group). The top 50 differentially expressed genes (DEG) upregulated and downregulated are shown in descending order of significance based on adjusted P-value (P adj ) for (A) female and (B) male lungs. DEG thresholds were set at Log2Foldchange > 1, P adj <0.05. Z-score coloring represents relative gene expression across all groups. Samples are sorted by complete hierarchical clustering. Gene Ontology (GO) analysis for (C) Female and (D) Male samples are shown as the top 20 gene ontologies in descending order of P adj . The X-axis represents the number of DEGs in this comparison that underlies the significant GO.

Article Snippet: Cav1 -/- (Cav1 tm1Mls /J) and B6/129SJ2 wild-type control mice were originally purchased from Jackson Labs. Cav1-RC mice ( ) were obtained from William Sessa, Yale University.

Techniques: Comparison, Knock-Out, Gene Expression

Journal: Frontiers in Physiology

Article Title: Transcriptomic profiling of the sex-linked biological pathways of severe pulmonary arterial hypertension associated with endothelial cell caveolin-1 depletion and chronic hypoxia

doi: 10.3389/fphys.2026.1794886

Figure Lengend Snippet: Summary of the effect of Caveolin-1 (Cav1) genetic status, hypoxia, and sex on the expression of known pulmonary arterial hypertension (PAH) risk factors and summary figure of transcriptional changes found in Cav1 genetic modulation. (A) A heatmap of genes associated with heritable PAH risk. Each group represents the average expression of these genes across all samples in the group. Genes are organized by hierarchical clustering to demonstrate similar patterns of expression across the groups. (n = 2 – 3) (B) Summary figure showing which transcriptional pathways are modulated during global Cav1 knockout or endothelial Cav1 reconstitution. Gene ontologies are distinguished by which sex, or both, they show significant change.

Article Snippet: Cav1 -/- (Cav1 tm1Mls /J) and B6/129SJ2 wild-type control mice were originally purchased from Jackson Labs. Cav1-RC mice ( ) were obtained from William Sessa, Yale University.

Techniques: Expressing, Knock-Out