Real Time PCR and Sirius red-Fast Green staining.

<p><b>(a)</b> mRNA expression of Col1A1 and <b>(b)</b> α-SMA. <b>(c)</b> Collagen protein quantification.</p

Urinary excretion of nitrites in <i>Sol-Eng</i>^<i>+</i> and control mice.

<p>Urinary excretion of nitrites was measured in urine from <i>Sol-Eng</i>^<i>+</i> and control mice collected in metabolic cages, and corrected by creatinine concentration. Data are shown as mean ± S.E.M. Unpaired t-test.</p

Hepatic and aortae histological findings.

<p>Hepatic histopathological analysis. <b>(b-e)</b> Representative images of Hematoxylin-Eosin staining progression of HFHC group over the time <i>vs</i>. CTRL <b>(a).</b> Higher magnification of the dashed area <b>(f-j). (l-o)</b> Gömöri trichrome staining for collagen of HFHC group over the time <i>vs</i>. CTRL <b>(k)</b>. <b>(p, q)</b> Representative picture of Hematoxylin & Eosin staining in aortae of controls <b>(p)</b> and HFHC group <b>(q).</b> In all pictures scale bar is 100 μm.</p

Concentrations of human soluble endoglin in plasma of <i>Sol-Eng</i>^<i>+</i> and control mice.

<p>Human soluble endoglin concentrations in plasma from female (control n = 53, <i>Sol-Eng</i>^<i>+</i> n = 22) (A) and male (control n = 31, <i>Sol-Eng</i>^<i>+</i> n = 19) (B) mice. Data are shown as mean ± S.E.M. Mann-Whitney test, ***p≤0.001.</p

Glucose and insulin quantification in males and females.

<p>^a p<0.05, ^b p<0.01, ^c p<0.001, ns: not statistically relevant. Mean ± SD <i>vs</i>. age and sex matched CTRL.</p

Lipid profile analysis and serum ALT.

<p><b>(a)</b> Total cholesterol. <b>(b)</b> HDL-C. <b>(c)</b> LDL-C. <b>(d)</b> Triglycerides. <b>(e)</b> ALT. Data are expressed as mean ± SD. Statistical significance was calculated <i>vs</i>. age and sex matched CTRL. * p<0.05, ** p<0.01, *** p<0.001.</p

Blood pressure (A) and heart rate (B) in <i>Sol-Eng</i>^<i>+</i> and control male mice assessed by telemetry.

<p>SABP: Systolic arterial blood pressure; DABP: Diastolic arterial blood pressure; MABP: mean arterial blood pressure. Data are shown as mean ± S.E.M. ANOVA and unpaired t-test with respect to control mice, *p≤0.01.</p

Endothelium-dependent responses in <i>Sol-Eng</i>^<i>+</i> and control mice.

<p>Acetylcholine-induced relaxation in PHE or PGF2α (1 μM) pre-constricted vessels (A). Effect of L-NAME on the PHE (1 μM)-induced contraction (B). Data are shown as mean ± S.E.M. Mann-Whitney test, unpaired t-test, *p≤0.05, ***p≤0.001.</p

Histopathological findings.

<p>Histological analysis of the liver at each experimental checkpoint times according to Brunt's classification. Data is expressed as score/grade and between brackets the occurrence.</p

Impaired vascular contractility in female <i>Sol-Eng</i>^<i>+</i> mice as compared to control mice.

<p>Maximal contraction to KCl (30 mM) (A). Maximal contraction to PGF2α (10μM) (B) and to PHE (1 μM) (C) in <i>Sol-Eng</i>^<i>+</i> and control mice. Comparison of dose-response to PGF2α (D) and PHE (E) in <i>Sol-Eng</i>^<i>+</i> as compared to control mice. Data are shown as mean ± S.E.M. Unpaired t-test, **p≤0.01, ***p≤0.001.</p