Figure 1 - uploaded by Silvia Fittipaldi
Content may be subject to copyright.
Carotid artery calcifications, hematoxylin and eosin staining. A: Sheet-like calcifications; B: Osteocytes are visible within the bone lacunae-like mature structure in development with lamellar bone. L: Lumen; FC: Fibrous cap; Arrowhead: Ossification; O: Osteocytes.
Source publication
The term ''Stammzelle'' (stem cells) originally appeared in 1868 in the works of Ernst Haeckel who used it to describe the ancestor unicellular organism from which he presumed all multicellular organisms evolved. Since then stem cells have been studied in a wide spectrum of normal and pathological conditions; it is remarkable to note that ectopic a...
Context in source publication
Context 1
... some cases arteries can evolve into mature bone tissue histomorphologically indistinguishable from skel- etal bone [11] . In our practice, this evolution occurs in at least 5% of diseased arteries. In Figure 1, a Haematoxy- lin-Eosin staining of a section of carotid atherosclerotic plaques revealed the presence of osteocyte cells within bone lacunae-like mature structure in development; la- mellar bone is also ...
Citations
... 13 Since Ernst Haeckel proposed the concept of stem cells in 1868, the exploration of stem cells and their application in diseases have been the focus of scientific research and clinical practice. 14 Indeed, they hold significant implications in the treatment of various diseases and have considerably promoted the development of regenerative medicine. 15 The application of stem cells in ED started later, with no corresponding reports published until the 21st century. ...
... It was followed by several Chinese institutions followed, such as Sun Yat-sen University (26), Shanghai Jiao Tong University (24), and Peking University (21). It is worthwhile mentioning that while Nanjing University did not publish many articles (14), it ranked first in ACI (50.3), signifying that the documents produced by this institution were published earlier or of higher quality. Furthermore, a visual analysis of the institutions was implemented to generate a collaborative network ( Figure 3B). ...
... (28), indicating that this is a popular journal for research in this field. It was followed by the International Journal of Impotence Research (28), Andrology (20), Asian Journal of Andrology (18), and Translational Andrology and Urology (14), which are all professional journals related to urology and andrology. Moreover, the 2022 impact factors (IF) of these journals were all slightly low, ranging from 2.5 to 5.5, which may be limited by the average IF level of professional journals in the field of andrology. ...
Purpose
As a common male disease, erectile dysfunction (ED) seriously affects the physical and mental health of patients. In recent years, studies have continued to point out the great potential of stem cell therapy (SCT) in the treatment of ED. The purpose of this study is to comprehensively analyze the research of SCT for ED and understand the development trends and research frontiers in this field.
Methods
Publications regarding SCT and ED were retrieved and collected from the Web of Science Core Collection. CiteSpace and VOSviewer software were then utilized for bibliometric and visualization analysis.
Results
A total of 524 publications were eventually included in this study. The annual number of publications in this field was increasing year by year. China and the USA were the two most productive countries. Lin GT, Lue TF and Lin CS, and the University of California San Francisco where they worked were the most productive research group and institution, respectively. The journal with the largest number of publications was The Journal of Sexual Medicine, and the following were mostly professional journals of urology and andrology. Diabetes mellitus-induced ED and cavernous nerve injury-related ED were the two most commonly constructed models of ED in studies. Concerning the types of stem cells, mesenchymal stem cells derived from adipose and bone marrow were most frequently used. Moreover, future research would mainly focus on exosomes, tissue engineering technology, extracorporeal shockwave therapy, and clinical translation.
Conclusion
The research of SCT for ED will receive increasing global attention in the future. Our study provided bibliometric and visualization analysis of published literature, helping researchers understand the global landscape and frontiers in this field. More preclinical and clinical studies should be conducted to more deeply explore the underlying mechanisms of treatment and promote clinical translation.
... The mechanism of arterial calcification is still largely unknown. Different pathogenetic mechanisms are reported to be involved: genetic factors as in the model of pseudoxantoma elasticum (D'Marco et al., 2020), epigenetic factors fueling atherosclerosis (Kwon et al., 2020), changes in transcriptional and posttranscriptional regulation control, as miRNA-mRNA axis (Vasuri et al., 2020), injuries leading to vascular wall necrosis and inflammation, differentiation of resident or circulating vascular progenitors (Psaltis et al., 2014;Vasuri et al., 2014), metabolic factors (Demer and Tintut, 2014), and local context factors. This heterogeneity may account for the presence of different vascular calcification disease morphologies and phenotypes. ...
Bone development-related genes are enriched in healthy femoral arteries, which are more prone to calcification, as documented by the predominance of fibrocalcific plaques at the femoral location. We undertook a prospective histological study on the presence of calcifications in normal femoral arteries collected from donors. Since endothelial-to-mesenchymal transition (EndMT) participates in vascular remodeling, immunohistochemical (IHC) and molecular markers of EndMT and chondro-osteogenic differentiation were assessed. Transmission electron microscopy (TEM) was used to describe calcification at its inception. Two hundred and fourteen femoral arteries were enrolled. The mean age of the donors was 39.9 ± 12.9 years; male gender prevailed (M: 128). Histology showed a normal architecture; calcifications were found in 52 (24.3%) cases, without correlations with cardiovascular risk factors. Calcifications were seen on or just beneath the inner elastic lamina (IEL). At IHC, SLUG was increasingly expressed in the wall of focally calcified femoral arteries (FCFA). ETS-related gene (ERG), SLUG, CD44, and SOX-9 were positive in calcifications. RT-PCR showed increased levels of BPM-2, RUNX-2, alkaline phosphatase, and osteocalcin osteogenic transcripts and increased expression of the chondrogenic marker, SOX-9, in FCFA. TEM documented osteoblast-like cells adjacent to the IEL, releasing calcifying vesicles from the cell membrane. The vesicles were embedded in a proteoglycan-rich matrix and were entrapped in IEL fenestrations. In this study, ERG- and CD44-positive cell populations were found in the context of increased SLUG expression, thus supporting the participation of EndMT in FCFA; the increased transcript expression of osteochondrogenic markers, particularly SOX-9, reinforced the view that EndMT, osteochondrogenesis, and neoangiogenesis interact in the process of arterial calcification. Given its role as a transcription factor in the regulation of endothelial homeostasis, arterial ERG expression can be a clue of endothelial dysregulation and changes in IEL organization which can ultimately hinder calcifying vesicle diffusion through the IEL fenestrae. These results may have a broader implication for understanding arterial calcification within a disease context.
... It occurs prevalently in aging and primary chronic conditions (hypertension, diabetes mellitus and chronic kidney disease), representing an important risk factor for cardiovascular morbidity and mortality [5][6][7][8]. Previously, the calcification of the vessel wall was known as a passive, degenerative and uncontrolled process caused only by the abnormal precipitation of calcium crystal in the vasculature [9,10]. Nowadays, a growing body of evidence suggests that it is an active, regulated event that shares similar characteristics with bone formation and metabolism. ...
... The term VitK2 indicates a family of bioactive isoprenologs, also called "menaquinones" (MKs), which differ from each other with respect to the number of isoprenoid units in the side chain [32]. Thus, it is generally denoted as MK-n, where "n" (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) is the number of isoprenoid residues in the side chain [43][44][45]; for example, the isoforms menaquinone-4 (MK-4) and menaquinone-7 (MK-7) present four and seven isoprenoid units, respectively [43]. ...
Osteoporosis (OP) and vascular calcification (VC) represent relevant health problems that frequently coexist in the elderly population. Traditionally, they have been considered independent processes, and mainly age-related. However, an increasing number of studies have reported their possible direct correlation, commonly defined as “bone-vascular crosstalk”. Vitamin K2 (VitK2), a family of several natural isoforms also known as menaquinones (MK), has recently received particular attention for its role in maintaining calcium homeostasis. In particular, VitK2 deficiency seems to be responsible of the so-called “calcium paradox” phenomenon, characterized by low calcium deposition in the bone and its accumulation in the vessel wall. Since these events may have important clinical consequences, and the role of VitK2 in bone-vascular crosstalk has only partially been explained, this review focuses on its effects on the bone and vascular system by providing a more recent literature update. Overall, the findings reported here propose the VitK2 family as natural bioactive molecules that could be able to play an important role in the prevention of bone loss and vascular calcification, thus encouraging further in-depth studies to achieve its use as a dietary food supplement.
... The effect of sirolimus on mesenchymal cells is unknown, but it is an important issue, since mesenchymal cells such as myofibroblasts and cells promoting vascular calcification play an important role in atherogenesis and vascular restenosis [7,8]. In 2001 a preclinical study on a porcine model demonstrated that the use of a sirolimus-eluting stent (SES) reduced the in-stent neointimal hyperplasia of 35-50% [9]. ...
We evaluated the long-term effects of sirolimus on three different cell in vitro models, cultured in physiological conditions mimicking sirolimus-eluted stent, in order to clarify the effectiveness of sirolimus in blocking cell proliferation and survival.
Three cells lines (WPMY-1 myofibroblasts, HT-29 colorectal adenocarcinoma, and U2OS osteosarcoma) were selected and growth in 10 ml of Minimum Essential Medium for 5 weeks with serial dilutions of sirolimus. The number of colonies and the number of cells per colony were counted.
As main result, the number of WPMY-1 surviving colonies increased in a dose-dependent manner when treated with sirolimus (p = 0.0011), while the number of U2OS colonies progressively decreased (p = 0.0011). The clonal capacity of HT-29 was not modified by the exposure to sirolimus (p = 0.6679).
In conclusion sirolimus showed the well-known cytostatic effect, but with an effect on clonogenic potential different among the different cell types. In the practice, the plaque typology and composition may influence the response to sirolimus and thus the effectiveness of eluted stent.
... Structural and functional changes occur with age both in central and peripheral arteries, as suggested by clinical and preclinical data (Rubio-Ruiz et al., 2014). Arterial stiffness increases (Donato et al., 2018;Scuteri et al., 2008) due to: i) augmented conducted wave velocity or changes in the passive mechanical properties of the artery that reduces its compliance; ii) molecular and cellular alterations of artery wall, leading to impaired endothelial function, chronic vascular inflammation, and calcification (Libby et al., 2019;Vasuri et al., 2014). All these modifications result in a complex dysregulation including microvascular perfusion and alterations of the extracellular matrix along with the effects of inflammatory and atherogenic responses. ...
Atherosclerosis is considered a chronic inflammatory disease of arteries associated with the aging process. Many risk factors have been identified and they are mainly related to life-styles, gene-environment interactions and socioeconomic status. Carotid and coronary artery diseases are the two major atherosclerotic conditions, being the primary cause of stroke and heart attack, respectively. Nevertheless, carotid plaque assumes particular aspects not only for the specific molecular mechanisms, but also for the types of atheroma which may be associated with a better or a worst prognosis. The identification of circulating blood biomarkers able to distinguish carotid plaque types (stable or vulnerable) is a crucial step for the improvement of adequate therapeutic approaches avoiding or delaying endarterectomy in the oldest old individuals (> 80 years), a population predicted to growth in the next years. The review highlights the most recent knowledge on carotid plaque molecular mechanisms, focusing on microRNAs (miRs), as a site-specific accelerated aging within the conceptual framework of Geroscience for new affordable therapies.
... The arterial calcification during atherosclerotic disease has been considered as a passive process for long time [1,2], albeit the recent literature recognized that vascular calcification is the consequence of a finely regulated mineral metabolism [1,3]. This process involves several cell types within the vessel wall or even circulating cells [3][4][5]. ...
... The arterial calcification during atherosclerotic disease has been considered as a passive process for long time [1,2], albeit the recent literature recognized that vascular calcification is the consequence of a finely regulated mineral metabolism [1,3]. This process involves several cell types within the vessel wall or even circulating cells [3][4][5]. ...
Arterial calcification is an actively regulated process, with different morphological manifestations. Micro-RNAs emerged as potential regulators of vascular calcification; they may become novel diagnostic tools and be used for a finest staging of the carotid plaque progression. The present study aimed at characterizing the different miRNA-mRNA axes in carotid plaques according to their histological patterns of calcification. Histopathological analysis was performed on 124 retrospective carotid plaques, with clinical data and preoperatory angio-CT. miRNA analysis was carried out with microfluidic cards. Real-time PCR was performed for selected miRNAs validation and for RUNX-2 and SOX-9 mRNA levels. CD31, CD68, SMA, and SOX-9 were analyzed by immunohistochemistry. miRNA levels on HUVEC cells were analyzed for confirming results under in vitro osteogenic conditions. Histopathological analysis revealed two main calcification subtypes of plaques: calcific cores (CC) and protruding nodules (PN). miRNA array and PCR validation of miR-1275, miR-30a-5p, and miR-30d indicated a significant upregulation of miR-30a-5p and miR-30d in the PN plaques. Likewise, the miRNA targets RUNX-2 and SOX-9 resulted poorly expressed in PN plaques. The inverse correlation between miRNA and RUNX-2 levels was confirmed on osteogenic-differentiated HUVEC. miR-30a-5p and miR-30d directly correlated with calcification extension and thickness at angio-CT imaging. Our study demonstrated the presence of two distinct morphological subtypes of calcification in carotid atheromatous plaques, supported by different miRNA signatures, and by different angio-CT features. These results shed the light on the use of miRNA as novel diagnostic markers, suggestive of plaque evolution.
... Chronic inflammation due to an aneurismal history cause a diminution of SMCs with vascular impairment and reduction of production of elastine and basement membrane. All of these findings cause the loss of organization of extracellular matrix [70, [144][145][146]. In neo-intimal lesions and adventitia of atherosclerotic plaques of human corps after autopsies several authors showed the presence of CD34+Sca1+CD133− cells. ...
Multipotent stem cells - such as mesenchymal stem/stromal cells and stem cells derived from different sources like vascular wall are intensely studied to try to rapidly translate their discovered features from bench to bedside. Vascular wall resident stem cells recruitment, differentiation, survival, proliferation, growth factor production, and signaling pathways transduced were analyzed. We studied biological properties of vascular resident stem cells and explored the relationship from several factors as Matrix Metalloproteinases (MMPs) and regulations of biological, translational and clinical features of these cells. In this review we described a translational and clinical approach to Adult Vascular Wall Resident Multipotent Vascular Stem Cells (VW-SCs) and reported their involvement in alternative clinical approach as cells based therapy in vascular disease like arterial aneurysms or peripheral arterial obstructive disease.
... In addition to the cells surrounding the vasculature, there are several types of circulating progenitor cells participating in VC formation [32,33]. Patients with elevated glycated hemoglobin had a higher percentage of circulating endothelial progenitor cells, which potentially mediated diabetic vasculopathy especially VC [34]. ...
A series of clinical trials have confirmed the correlation between vascular calcification (VC) and cardiovascular events and mortality. However, current treatments have little effects on the regression of VC. Potent and illustrative mechanisms have been proven to exist in both bone metabolism and VC, indicating that these two processes share similarities in onset and progression. Multiple osteoblast-like cells and signaling pathways are involved in the process of VC. In this review, we summarized the roles of different osteoblast-like cells and we emphasized on how they communicated and interacted with each other using different signaling pathways. Further studies are needed to uncover the underlying mechanisms and to provide novel therapies for VC.
... The most recent mechanism proposed to elucidate arterial calcification is the possible role of resident or circulating stem cells that differentiate into chondro-osteogenic cells [3]. Nowadays, the clinical impact of arterial calcification is still unclear [4]; indeed the extent of calcification is associated with either a good or bad prognosis. For example, in the coronary arteries small calcifications increase the risk of plaque rupture whereas bigger deposits seem to stabilize the plaque [5]. ...
Background:
Calcifications of atherosclerotic plaques represent a controversial issue as they either lead to the stabilization or rupture of the lesion. However, the cellular key players involved in the progression of the calcified plaques have not yet been described. The primary reason for this lacuna is that decalcification procedures impair protein and nucleic acids contained in the calcified tissue. The aim of our study was to preserve the cellular content of heavily calcified plaques with a new rapid fixation in order to simplify the study of calcifications.
Methods:
Here we applied a fixation method for fresh calcified tissue using the Carnoy's solution followed by an enzymatic tissue digestion with type II collagenase. Immunohistochemistry was performed to verify the preservation of nuclear and cytoplasmic antigens. DNA content and RNA preservation was evaluated respectively with Feulgen staining and RT-PCR. A checklist of steps for successful image analysis was provided. To present the basic features of the F-DNA analysis we used descriptive statistics, skewness and kurtosis. Differences in DNA content were analysed with Kruskal-Wallis and Dunn's post tests. The value of P < 0.05 was considered significant.
Results:
Twenty-four vascular adult tissues, sorted as calcified (14) or uncalcified (10), were processed and 17 fetal tissues were used as controls (9 soft and 8 hard). Cells composing the calcified carotid plaques were positive to Desmin, Vimentin, Osteocalcin or Ki-67; the cellular population included smooth muscle cells, osteoblasts and osteoclasts-like cells and metakaryotic cells. The DNA content of each cell type found in the calcified carotid artery was successfully quantified in 7 selected samples. Notably the protocol revealed that DNA content in osteoblasts in fetal control tissues exhibits about half (3.0 ng) of the normal nuclear DNA content (6.0 ng).
Conclusion:
Together with standard histology, this technique could give additional information on the cellular content of calcified plaques and help clarify the calcification process during atherosclerosis.
... The presence of heterotopic calcification in the arterial wall occurs frequently with advanced age, as well as pathological conditions, such as chronic kidney disease and type II diabetes mellitus (Moe and Chen 2004;Shao et al. 2010). Histologically, arterial calcifications is classified as intimal (especially related to atherosclerosis) and medial, unrelated to atherosclerosis (Monckeberg's type) (Karwowski et al. 2012;Vasuri et al. 2014). The intimal calcifications are the most common form. ...
Little is known about the real incidence and the clinical relevance of the enigmatic Monckeberg's medial calcification in the patency of the femoral artery allograft. Here we present a retrospective study on 143 multiorgan donors (mean age 38 years, range 14-59 years), to describe the incidence and the morphological features of vascular calcifications in banked femoral arteries suitable for clinical use. In the present series, focal vascular calcifications were present in 36 (25 %) cases, 23 cases localized in the intima, 7 in the media, and 6 were mixed. No correlation was found between the incidence of calcifications and the classical cardiovascular clinical risk factors (n = 9); only hypertension correlated with the medial localization, but not with the incidence, of the calcification (P = 0.017). While the macroscopic exclusion criteria of vascular grafts include atheromatous and not-atheromatous lesions, we ignore the actual impact of Monckeberg's medial calcification on vessel transplantation and allograft life. In our opinion this is a very important topic, since when the histological criteria for Monckeberg's calcification diagnosis are used, 25 % of our young donors population was affected. Whether Monckeberg's medial calcification is a stable arterial condition, apparently underestimated in the general population, or a dynamic process evolving with age and atherosclerosis, or a banking-related vascular alteration, still remain an open issue deserving further studies with subjects of different ages.
