In the management of hypertension, only limited advances have been made over the past decades. Recent studies highlight the potential of next-generation incretin-based therapeutics, such as GLP-1 RAs (glucagon-like peptide-1 receptor agonists) like semaglutide and dual GLP-1/GIP (glucose-dependent insulinotropic polypeptide) receptor agonists like tirzepatide. These drugs not only promote weight loss but also substantially lower blood pressure (BP) and reduce cardiovascular end points. The extent to which incretin-based therapies improve disease outcomes via weight loss versus so-called direct tissue effects is the subject of great interest, not only for BP but also for other clinical outcomes. Although, incretin-based therapeutics were initially not designed to treat hypertension, clinical studies demonstrate an impressive reduction in BP in patients treated with these agents, with an even more pronounced effect in patients with obesity and hypertension. The current hypertension guide

BACKGROUND: ATP citrate lyase (ACLY) is a key enzyme in de novo lipogenesis that generates acetyl-CoA from citrate. Although fatty acids are required for energy production and biomass synthesis in the heart, the regulatory mechanisms of ACLY-mediated de novo lipogenesis in pathological cardiac fibroblasts remain unknown. The aim of this study was to investigate the biological role of ACLY in cardiac remodeling. METHODS: Adeno-associated virus serotype 9-mediated shRNA targeting Acly was intravenously injected into C57BL/6J male mice. The mice were subsequently continuously infused with a mixture of angiotensin II and phenylephrine. Cardiac phenotypes were evaluated via histological staining. Cell proliferation assays, stable isotope tracing with 13C-labeled glucose, and chromatin immunoprecipitation assays were performed using human cardiac fibroblasts. RESULTS: ACLY expression was upregulated in the heart sections of mice treated with angiotensin II/phenylephrine, in particular in fib

BACKGROUND: Arterial hypertension (HTN) and type 2 diabetes (T2DM) are contributors to chronic kidney disease leading to glomerulomegaly and podocyte loss. Enlarged glomeruli and podocyte depletion are associated with kidney disease progression. This retrospective study aimed to investigate morphometric changes in patients with HTN and the contribution of coexisting T2DM in HTN. METHODS: Glomerular and podocyte structure was estimated stereologically in unaffected areas of tumor nephrectomies in 99 patients. Morphometric features between subjects with HTN (n=47), HTN+T2DM (n=32), and controls without HTN and T2DM (n=20) were compared by ANOVA. Linear regression models evaluated the effect of morphometric parameters on renal compensation after nephrectomy (change of estimated glomerular filtration rate from pre-nephrectomy to 12 months post-nephrectomy). RESULTS: In total, 36% of the HTN and 50% of the patients with T2DM exhibited dipstick-positive proteinuria. Glomerular volume in HTN+

BACKGROUND: Primary aldosteronism (PA) is a distinct cause of low-renin hypertension (LRH), characterized by inappropriate aldosterone production. We investigated the distinction between LRH and PA by leveraging the physiological effects of angiotensin-converting enzyme inhibition. METHODS: We conducted a retrospective cohort study including 756 patients with LRH who underwent a captopril challenge test (CCT) for evaluation of PA. The distinction between PA and LRH was assessed using 4 CCT criteria: (1) Post-CCT plasma renin activity <1 ng/mL per hour and plasma aldosterone concentration decrease 30 ng/dL per ng/mL per hour; (3) Post-CCT plasma renin activity 11 ng/dL. Longitudinal outcomes following aldosterone-targeted therapy were assessed using the Primary Aldosteronism Surgery Outcome and Primary Aldosteronism Medical Outcome criteria. RESULTS: There was a con