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Background: Empagliflozin (empa), a selective sodium-glucose cotransporter (SGLT)2 inhibitor, reduced cardiovascular mortality and hospitalization for heart failure in patients with type 2 diabetes at high cardiovascular risk independent of glycemic control. The cardiovascular protective effect of empa was evaluated in an experimental model of metabolic syndrome, the obese ZSF1 rat, and its' lean control. Methods: Lean and obese ZSF1 rats were either non-treated or treated with empa (30 mg/kg/day) for 6 weeks. Vascular reactivity was assessed using mesenteric artery rings, systolic blood pressure by tail-cuff sphygmomanometry, heart function and structural changes by echocardiography, and protein expression levels by Western blot analysis. Results: Empa treatment reduced blood glucose levels from 275 to 196 mg/dl in obese ZSF1 rats whereas normoglycemia (134 mg/dl) was present in control lean ZSF1 rats and was unaffected by empa. Obese ZSF1 rats showed increased systolic blood pressure, and blunted endothelium-dependent relaxations associated with the appearance of endothelium-dependent contractile responses (EDCFs) compared to control lean rats. These effects were prevented by the empa treatment. Obese ZSF1 rats showed increased weight of the heart and of the left ventricle volume without the presence of diastolic or systolic dysfunction, which were improved by the empa treatment. An increased expression level of senescence markers (p53, p21, p16), tissue factor, VCAM-1, SGLT1 and SGLT2 and a down-regulation of eNOS were observed in the aortic inner curvature compared to the outer one in the control lean rats, which were prevented by the empa treatment. In the obese ZSF1 rats, no such effects were observed. The empa treatment reduced the increased body weight and weight of lungs, spleen, liver and perirenal fat, hyperglycemia and the increased levels of total cholesterol and triglycerides in obese ZSF1 rats, and increased blood ketone levels and urinary glucose excretion in control lean and obese ZSF1 rats. Conclusion: Empa reduced glucose levels by 28% and improved both endothelial function and cardiac remodeling in the obese ZSF1 rat. Empa also reduced the increased expression level of senescence, and atherothrombotic markers at arterial sites at risk in the control lean, but not obese, ZSF1 rat.

Purpose: Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening disease with often unrecognized inherited forms. We sought to identify novel pathogenic variants associated with autosomal dominant inheritance of TAAD. Methods: We analyzed exome sequencing data from 35 French TAAD families and performed next-generation sequencing capture panel of genes in 1114 unrelated TAAD patients. Functional effects of pathogenic variants identified were validated in cell, tissue, and mouse models. Results: We identified five functional variants in THSD4 of which two heterozygous variants lead to a premature termination codon. THSD4 encodes ADAMTSL6 (member of the ADAMTS/L superfamily), a microfibril-associated protein that promotes fibrillin-1 matrix assembly. The THSD4 variants studied lead to haploinsufficiency or impaired assembly of fibrillin-1 microfibrils. Thsd4 +/mice showed progressive dilation of the thoracic aorta. Histologic examination of aortic samples from a patient carrying a THSD4 variant and from Thsd4 +/mice, revealed typical medial degeneration and diffuse disruption of extracellular matrix. Conclusion: These findings highlight the role of ADAMTSL6 in aortic physiology and TAAD pathogenesis. They will improve TAAD management and help develop new targeted therapies.

Long-term outcomes of surgical procedures performed for popliteal artery entrapment syndrome can be considered satisfactory.

Hypertension is the leading cause of death in developed countries; its management is the subject of guidelines that are regularly reviewed and updated. However, the guidelines from France, the UK, Europe and the USA differ. Some recommendations are graded, whereas others are not. All recommendations emphasize the role of alternative methods for clinical measurement of blood pressure, such as ambulatory blood pressure measurement (ABPM) or self-measurement. The UK guideline recommends that the diagnosis of hypertension should be established by ABPM. The USA guideline recommends a target of ≤ 150/90 mmHg for patients aged >60 years. The French guideline recommends that the target blood pressure remains at <140/90 mmHg, with <150 mmHg for patients aged >80 years. Systolic blood pressure between 130 and 139 mmHg and diastolic blood pressure <90 mmHg are recommended for diabetic patients and those with chronic kidney disease. The French Society of Hypertension (SFHTA) guideline is unique in recommending a dedicated consultation to announce the diagnosis to the patient. In the French and European guidelines, diuretics, beta-blockers, calcium antagonists, angiotensin-converting enzyme (ACE) inhibitors and angiotensin II type 1 receptor blockers (ARBs) remain indicated as first-line therapy for hypertension; if the target blood pressure is not achieved, they recommend combining two active substances. The UK guideline recommends ACE inhibitors or ARBs as first-line therapy for patients aged <55 years; calcium antagonists are advised for patients aged >55 years and for black patients. The USA guideline advises treating non-black patients, including those with diabetes, with thiazides, calcium antagonists, ACE inhibitors or ARBs; for black patients, including those with diabetes, it recommends thiazide and calcium antagonists.

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