Hypertension-induced cardiac remodeling is a complex process driven by interconnected molecular and cellular mechanisms that culminate in hypertensive myocardium, characterized by ventricular hypertrophy, fibrosis, impaired angiogenesis, and myocardial dysfunction. This review discusses the histomorphometric changes in capillary density, fibrosis, and mast cells in the hypertensive myocardium and delves into the roles of key regulatory systems, including the apelinergic system, vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) pathways, and nitric oxide (NO)/nitric oxide synthase (NOS) signaling in the pathogenesis of hypertensive heart disease (HHD). Capillary rarefaction, a hallmark of HHD, contributes to myocardial ischemia and fibrosis, underscoring the importance of maintaining vascular integrity. Targeting capillary density (CD) through antihypertensive therapy or angiogenic interventions could significantly improve cardiac outcomes. Myocardial fibrosis, mediated by excessive collagen deposition and influenced by fibroblast growth factor-2 (FGF-2) and transforming growth factor-beta (TGF-β), plays a pivotal role in the structural remodeling of hypertensive myocardium. While renin–angiotensin–aldosterone system (RAAS) inhibitors show anti-fibrotic effects, more targeted therapies are needed to address fibrosis directly. Mast cells, though less studied in humans, emerge as critical regulators of cardiac remodeling through their release of pro-fibrotic mediators such as histamine, tryptase, and FGF-2. The apelinergic system emerges as a promising therapeutic target due to its vasodilatory, anti-fibrotic, and cardioprotective properties. The system counteracts the deleterious effects of the RAAS and has demonstrated efficacy in preclinical models of hypertension-induced cardiac damage. Despite its potential, human studies on apelin analogs remain limited, warranting further exploration to evaluate their clinical utility. VEGF signaling plays a dual role, facilitating angiogenesis and compensatory remodeling during the early stages of arterial hypertension (AH) but contributing to maladaptive changes when dysregulated. Modulating VEGF signaling through exercise or pharmacological interventions has shown promise in improving CD and mitigating hypertensive cardiac damage. However, VEGF inhibitors, commonly used in oncology, can exacerbate AH and endothelial dysfunction, highlighting the need for therapeutic caution. The NO/NOS pathway is essential for vascular homeostasis and the prevention of oxidative stress. Dysregulation of this pathway, particularly endothelial NOS (eNOS) uncoupling and inducible NOS (iNOS) overexpression, leads to endothelial dysfunction and nitrosative stress in hypertensive myocardium. Strategies to restore NO bioavailability, such as tetrahydrobiopterin (BH₄) supplementation and antioxidants, hold potential for therapeutic application but require further validation. Future studies should adopt a multidisciplinary approach to integrate molecular insights with clinical applications, paving the way for more personalized and effective treatments for HHD. Addressing these challenges will not only enhance the understanding of hypertensive myocardium but also improve patient outcomes and quality of life.

Angiogenesis, the natural mechanism by which fresh blood vessels develop from preexisting ones, is altered in arterial hypertension (AH), impacting renal function. Studies have shown that hypertension-induced renal damage involves changes in capillary density (CD), indicating alterations in vascularization. We aimed to elucidate the role of the apelin receptor (APLNR), neuronal nitric oxide synthase (nNOS), and vascular endothelial growth factor (VEGF) in hypertension-induced renal damage. We used two groups of spontaneously hypertensive rats aged 6 and 12 months, representing different stages of AH, and compared them to age-matched normotensive controls. The kidney tissue samples were prepared through a well-established protocol. All data analysis was conducted with a dedicated software program. APLNR was localized in tubular epithelial cells and the endothelial cells of the glomeruli, with higher expression in older SHRs. The localization of nNOS and VEGF was similar. The expression of APLNR and nNOS increased with AH progression, while VEGF levels decreased. CD was lower in young SHRs compared to controls and decreased significantly in older SHRs in comparison to age-matched controls. Our statistical analysis revealed significant differences in molecule expression between age groups and varying correlations between the expression of the three molecules and CD.

Diabetic kidney disease (DKD) is a leading cause of chronic kidney disease (CKD) and end-stage renal disease worldwide, affecting approximately 40% of individuals with type 2 diabetes (T2DM) and 30% of those with type 1 diabetes (T1DM). As the prevalence of diabetes continues to rise, the burden of DKD is expected to grow correspondingly. This review explores the roles of key molecular pathways, including the apelinergic system, vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) axis, and nitric oxide (NO)/nitric oxide synthase (NOS) signaling, in DKD pathogenesis and potential therapeutic applications. The apelinergic system, involving apelin and its receptor (APLNR), influences endothelial function, glucose metabolism, and renal health. Preclinical studies highlight its dual role in renal protection and injury through anti-inflammatory and antioxidant pathways, while other evidence suggests that it may exacerbate DKD through podocyte damage and angiogenesis. Similarly, the VEGF/VEGFR axis demonstrates a complex contribution to DKD, where VEGF-A promotes pathological angiogenesis and glomerular damage, but its inhibition requires careful modulation to prevent adverse effects. The NO/NOS system, integral to vascular and renal homeostasis, also exhibits altered activity in DKD, with reduced bioavailability linked to oxidative stress and inflammation. This review underscores the intricate interplay between these pathways in DKD, revealing both challenges and opportunities in their therapeutic targeting. Further research is essential to refine strategies and develop effective interventions for DKD management.

Background: Age-related macular degeneration (AMD) is a progressive, degenerative disease of the central retina. AMD is subdivided into “dry” (atrophic), “wet” (exudative), and neovascular (nAMD) forms. In recent years, the concepts about nAMD changed with the development of optical coherence tomography–angiography (OCT-A) and intravitreal anti-VEGF treatment. The aim of this study was to define the morphologic type of the neovascular membrane (NVM) before treatment with OCT-A and to register vascular remodeling after treatment with anti-VEGF. We also analyzed the relationship between NVM and visual acuity. Methods: The study was retrospective and included 119 patients with newly diagnosed, treatment-naïve nAMD. All the patients underwent full ophthalmic examination and also fluoresceine angiography and optical coherence tomography–angiography (OCT-A). Results: Based on the collected data, we found repetitive regularities. Conclusion: The analysis of our results could be used as prognostic markers for the evolution of the disease and as a basis for new treatment strategies, depending on the naïve NVM morphologic type.