Systemic vasculopathy has occasionally been reported in cases of moyamoya disease (MMD). Since the pathological relationship between moyamoya vasculopathy (MMV) and moyamoya-related systemic vasculopathy (MMRSV) remains unclear, it was examined herein by a review of histopathologic studies in consideration of clinicopathological and genetic viewpoints. Although luminal stenosis was a common finding in MMV and MMRSV, histopathologic findings of vascular remodeling markedly differed. MMV showed intimal hyperplasia, marked medial atrophy, and redundant tortuosity of the internal elastic lamina, with outer diameter narrowing called negative remodeling. MMRSV showed hyperplasia, mainly in the intima and sometimes in the media, with disrupted stratification of the internal elastic lamina. Systemic vasculopathy has also been observed in patients with non-MMD carrying the RNF213 (ring finger protein 213) mutation, leading to the concept of RNF213 vasculopathy. RNF213 vasculopathy in patients with non-MMD was histopathologically similar to MMRSV. Cases of MMRSV have sometimes been diagnosed with fibromuscular dysplasia. Fibromuscular dysplasia is similar to MMD not only in the histopathologic findings of MMRSV but also from clinicopathological and genetic viewpoints. The significant histopathologic difference between MMV and MMRSV may be attributed to a difference in the original vascular wall structure and its resistance to pathological stress between the intracranial and systemic arteries. To understand the pathogeneses of MMD and MMRSV, a broader perspective that includes RNF213 vasculopathy and fibromuscular dysplasia as well as an examination of the 2- or multiple-hit theory consisting of genetic factors, vascular structural conditions, and vascular environmental factors, such as blood immune cells and hemodynamics, are needed.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a fatal disease caused by pulmonary vascular remodeling, with a high incidence and mortality. At present, many clinical drugs for treating PAH mainly exert effects by relaxing the pulmonary artery, with limited therapeutic effects, so the search for viable therapeutic agents continues uninterrupted. In recent years, natural flavonoids have shown promising potential in the treatment of cardiovascular diseases. It is necessary to comprehensively elucidate the potential of natural flavonoids to combat PAH.
OBJECTIVE: To evaluate the potential of natural flavonoids to hinder or slow down the occurrence and development of PAH, and to identify promising drug discovery candidates.
METHODS: Literature was collected from PubMed, Science Direct, Web of science, CNKI databases and Google scholar. The search terms used included \"pulmonary arterial hypertension\", \"pulmonary hypertension\", \"natural products\", \"natural flavonoids\", \"traditional chinese medicine\", etc., and several combinations of these keywords.
RESULTS: The resources, structural characteristics, mechanisms, potential and prospect strategies of natural flavonoids for treating PAH were summarized. Natural flavonoids offer different solutions as possible treatments for PAH. These mechanisms may involve various pathways and molecular targets related to the pathogenesis of PAH, such as inflammation, oxidative stress, vascular remodeling, genetic, ion channels, cell proliferation and autophagy. In addition, prospect strategies of natural flavonoids for anti-PAH including structural modification and nanomaterial delivery systems have been explored. This review suggests that the potential of natural flavonoids as alternative therapeutic agents in the prevention and treatment of PAH holds promise for future research and clinical applications.
CONCLUSIONS: Despite displaying the enormous potential of flavonoids in PAH, some limitations need to be further explored. Firstly, using advanced drug discovery tools, including computer-aided design and high-throughput screening, to further investigate the safety, biological activity, and precise mechanism of action of flavonoids. Secondly, exploring the structural modifications of these compounds is expected to optimize their efficacy. Lastly, it is necessary to conduct well controlled clinical trials and a comprehensive evaluation of potential side effects to determine their effectiveness and safety.

The clinical presentation, treatment history, and outcomes of two patients with posttraumatic arteriovenous fistula (PTAVF) were analyzed and compared with the pathological tissues of patients with hemodialysis arteriovenous fistula (HAVF). A search of the biomedical literature database (PubMed), using the keywords \" lower extremity\" and \"PTAVF,\" was conducted to obtain results and review the data. Postoperative histological analysis of patients with PTAVF showed differences from that of HAVF. The literature screening and analysis revealed that PTAVF is a chronic progressive process, with 70% of patients diagnosed after 3 months. The choice of treatment revealed that 20% of patients had severe complications and all were treated endovascularly. Due to the abnormal fistula of PTAVF and its specific histopathological features, the disease is not self-limiting. It is unwise to wait for PTAVF to cause \"failure.\" We recommend early and timely cure of this disease by surgery to avoid serious complications.

Over the past 40 years, there has been a strong focus on the development of mathematical models of angiogenesis, while developmental remodelling has received little such attention from the mathematical community. Sprouting angiogenesis can be seen as a very crude way of laying out a primitive vessel network (the raw material), while remodelling (understood as pruning of redundant vessels, diameter control, and the establishment of vessel identity and hierarchy) is the key to turning that primitive network into a functional network. This multiscale problem is of prime importance in the development of a functional vasculature. In addition, defective remodelling (either during developmental remodelling or due to a reactivation of the remodelling programme caused by an injury) is associated with a significant number of diseases. In this review, we discuss existing mathematical models of developmental remodelling and explore the important contributions that these models have made to the field of vascular development. These mathematical models are effectively used to investigate and predict vascular development and are able to reproduce experimentally observable results. Moreover, these models provide a useful means of hypothesis generation and can explain the underlying mechanisms driving the observed structural and functional network development. However, developmental vascular remodelling is still a relatively new area in mathematical biology, and many biological questions remain unanswered. In this review, we present the existing modelling paradigms and define the key challenges for the field.

Reducing low-density lipoprotein cholesterol (LDL-C) levels is a key target for lowering cardiovascular risk and preventing atherosclerotic cardiovascular disease (ASCVD). Red yeast rice (RYR) is a nutraceutical widely used as a lipid-lowering dietary supplement. The main cholesterol-lowering components of RYR are monacolins, particularly monacolin K, which is structurally identical to lovastatin and targets the same key enzyme of cholesterol biosynthesis. RYR supplementation reduces LDL-C levels by approximately 15-34% versus placebo, with a similar effect to low-dose, first-generation statins in subjects with mild-to-moderate dyslipidemia. RYR has also demonstrated beneficial reductions of up to 45% versus placebo in the risk of ASCVD events in secondary prevention studies. RYR at a dose that provides about 3 mg/d of monacolin K is well tolerated, with an adverse event profile similar to that of low-dose statins. RYR is therefore a treatment option for lowering LDL-C levels and ASCVD risk for people with mild-to-moderate hypercholesterolemia who are ineligible for statin therapy, particularly those who are unable to implement lifestyle modifications, and also for people who are eligible for statin therapy but who are unwilling to take a pharmacologic therapy.

Liver fibrosis could be the last hope for treating liver cancer and remodeling of the hepatic microenvironment has emerged as a strategy to promote the ablation of liver fibrosis. In recent years, especially with the rapid development of nanomedicine, hepatic microenvironment therapy has been widely researched in studies concerning liver cancer and fibrosis. In this comprehensive review, we summarized recent advances in nano therapy-based remodeling of the hepatic microenvironment. Firstly, we discussed novel strategies for regulatory immune suppression caused by capillarization of liver sinusoidal endothelial cells (LSECs) and macrophage polarization. Furthermore, metabolic reprogramming and extracellular matrix (ECM) deposition are caused by the activation of hepatic stellate cells (HSCs). In addition, recent advances in ROS, hypoxia, and impaired vascular remodeling in the hepatic fibrotic microenvironment due to ECM deposition have also been summarized. Finally, emerging nanotherapeutic approaches based on correlated signals were discussed in this review. We have proposed novel strategies such as engineered nanotherapeutics targeting antigen-presenting cells (APCs) or direct targeting T cells in liver fibrotic immunotherapy to be used in preventing liver fibrosis. In summary, this comprehensive review illustrated the opportunities in drug targeting and nanomedicine, and the current challenges to be addressed.

Cellular memory is a controversial concept representing the ability of cells to \"write and memorize\" stressful experiences via epigenetic operators. The progressive course of chronic, non-communicable diseases such as type 2 diabetes mellitus, cancer, and arteriosclerosis, is likely driven through an abnormal epigenetic reprogramming, fostering the hypothesis of a cellular pathologic memory. Accordingly, cultured diabetic and cancer patient-derived cells recall behavioral traits as when in the donor\'s organism irrespective to culture time and conditions. Here, we analyze the data of studies conducted by our group and led by a cascade of hypothesis, in which we aimed to validate the hypothetical existence and transmissibility of a cellular pathologic memory in diabetes, arteriosclerotic peripheral arterial disease, and cancer. These experiments were based on the administration to otherwise healthy animals of cell-free filtrates prepared from human pathologic tissue samples representative of each disease condition. The administration of each pathologic tissue homogenate consistently induced the faithful recapitulation of: (1) Diabetic archetypical changes in cutaneous arterioles and nerves. (2) Non-thrombotic arteriosclerotic thickening, collagenous arterial encroachment, aberrant angiogenesis, and vascular remodeling. (3) Pre-malignant and malignant epithelial and mesenchymal tumors in different organs; all evocative of the donor\'s tissue histopathology and with no barriers for interspecies transmission. We hypothesize that homogenates contain pathologic tissue memory codes represented in soluble drivers that \"infiltrate\" host\'s animal cells, and ultimately impose their phenotypic signatures. The identification and validation of the actors in behind may pave the way for future therapies.

Although the gold-standard method for the assessment of structural alteration in small resistance arteries is the evaluation of the MLR by micromyography in bioptic tissues, new, noninvasive techniques are presently under development, focusing mainly on the evaluation of WLR in retinal arterioles. These approaches represent a promising and interesting future perspective. Appropriate antihypertensive treatment is able to prevent the development of microvascular alterations or to induce their regression. Also, conductance arteries may be affected by a remodeling process in hypertension, and a cross-talk may exist between structural changes in the small and large arteries. In conclusion, the evaluation of microvascular structure is ready for clinical prime time, and it could, in the future, represent an evaluation to be performed in the majority of hypertensive patients, to better stratify cardiovascular risk and better evaluate the effects of antihypertensive therapy. However, for this purpose, we need a clear demonstration of the prognostic relevance of noninvasive measures of microvascular structure, in basal conditions and during treatment. Vascular remodeling may be frequently observed in hypertension, as well as in obesity and diabetes mellitus. An increased media to lumen ratio (MLR) or wall to lumen ratio (WLR) in microvessels is the hallmark of hypertension, and may impair organ flow reserve, being relevant in the maintenance and, probably, also in the progressive worsening of hypertensive disease, as well as in the development of hypertension-mediated organ damage/cardiovascular events. The molecular mechanisms underlying the development of vascular remodeling are only partly understood.

Cardiac remodelling is characterized by abnormal changes in the function and morphological properties such as diameter, mass, normal diameter of cavities, heart shape, fibrosis, thickening of vessels and heart layers, cardiomyopathy, infiltration of inflammatory cells, and some others. These damages are associated with damage to systolic and diastolic abnormalities, damage to ventricular function, and vascular remodelling, which may lead to heart failure and death. Exposure of the heart to radiation or anti-cancer drugs including chemotherapy drugs such as doxorubicin, receptor tyrosine kinase inhibitors (RTKIs) such as imatinib, and immune checkpoint inhibitors (ICIs) can induce several abnormal changes in the heart structure and function through the induction of inflammation and fibrosis, vascular remodelling, hypertrophy, and some others. This review aims to explain the basic mechanisms behind cardiac remodelling following cancer therapy by different anti-cancer modalities.

Cardiac allograft vasculopathy (CAV) is a pathologic immune-mediated remodelling of the vasculature in transplanted hearts and, by impairing perfusion, is the major cause of late graft loss. Although best understood following cardiac transplantation, similar forms of allograft vasculopathy occur in other vascularized organ grafts and some features of CAV may be shared with other immune-mediated vasculopathies. Here, we describe the incidence and diagnosis, the nature of the vascular remodelling, immune and non-immune contributions to pathogenesis, current therapies, and future areas of research in CAV.