Resident macrophages orchestrate homeostatic, inflammatory, and reparative activities. It is appreciated that different tissues instruct specialized macrophage functions. However, individual tissues contain heterogeneous subpopulations, and how these subpopulations are related is unclear.
View Article and Find Full Text PDFHypertension affects one-third of the world's population, leading to cardiac dysfunction that is modulated by resident and recruited immune cells. Cardiomyocyte growth and increased cardiac mass are essential to withstand hypertensive stress; however, whether immune cells are involved in this compensatory cardioprotective process is unclear. In normotensive animals, single-cell transcriptomics of fate-mapped self-renewing cardiac resident macrophages (RMs) revealed transcriptionally diverse cell states with a core repertoire of reparative gene programs, including high expression of insulin-like growth factor-1 (Igf1).
View Article and Find Full Text PDFRationale: Bone marrow transplantation (BMT) is used frequently to study the role of hematopoietic cells in atherosclerosis, but aortic arch lesions are smaller in mice after BMT.
Objective: To identify the earliest stage of atherosclerosis inhibited by BMT and elucidate potential mechanisms.
Methods And Results: mice underwent total body γ-irradiation, bone marrow reconstitution, and 6-week recovery.
High dimensional approaches that characterize single cells at unprecedented depth have helped uncover unappreciated heterogeneity, a better understanding of myeloid cell origins, developmental relationships and functions. These advancements are particularly important in cardiovascular disease, which remains the leading cause of death worldwide. Gradual, monocyte-dependent inflammatory processes, such as the development of atherosclerotic plaque within arterial vessels, contrasts with the robust acute response within the myocardium that occurs when a vessel is occluded.
View Article and Find Full Text PDFIn the version of this article initially published, the equal contribution of the third author was omitted. The footnote links for that author should be "Sara Nejat" and the correct statement is as follows: "These authors contributed equally: Sarah A. Dick, Jillian A.
View Article and Find Full Text PDFMacrophages promote both injury and repair after myocardial infarction, but discriminating functions within mixed populations remains challenging. Here we used fate mapping, parabiosis and single-cell transcriptomics to demonstrate that at steady state, TIMD4LYVE1MHC-IICCR2 resident cardiac macrophages self-renew with negligible blood monocyte input. Monocytes partially replaced resident TIMD4LYVE1MHC-IICCR2 macrophages and fully replaced TIMD4LYVE1MHC-IICCR2 macrophages, revealing a hierarchy of monocyte contribution to functionally distinct macrophage subsets.
View Article and Find Full Text PDFMuscle-enriched lamin-interacting protein () is an alternatively spliced gene whose splicing specificity is dictated by tissue type. MLIP is most abundantly expressed in brain, cardiac, and skeletal muscle. In the present study, we systematically mapped the transcriptional start and stop sites of murine Rapid amplification of cDNA ends (RACE) of transcripts from the brain, heart, and skeletal muscle revealed two transcriptional start sites (TSSs), exon 1a and exon 1b, and only one transcriptional termination site.
View Article and Find Full Text PDFInnate and adaptive immune cells modulate heart failure pathogenesis during viral myocarditis, yet their identities and functions remain poorly defined. We utilized a combination of genetic fate mapping, parabiotic, transcriptional, and functional analyses and demonstrated that the heart contained two major conventional dendritic cell (cDC) subsets, CD103 and CD11b, which differentially relied on local proliferation and precursor recruitment to maintain their tissue residency. Following viral infection of the myocardium, cDCs accumulated in the heart coincident with monocyte infiltration and loss of resident reparative embryonic-derived cardiac macrophages.
View Article and Find Full Text PDFHispanics in the United States experience significant health disparities. Using focus groups conducted in Spanish, we explored the perspectives of 172 Hispanic adults regarding their healthcare experiences. Many participants were women (64.
View Article and Find Full Text PDFAs a greater proportion of patients survive their initial cardiac insult, medical systems worldwide are being faced with an ever-growing need to understand the mechanisms behind the pathogenesis of chronic heart failure (HF). There is a wealth of information about the role of inflammatory cells and pathways during acute injury and the reparative processes that are subsequently activated. We discuss the different causes that lead to chronic HF development and how the sum of initial inflammatory and reparative responses only sets the trajectory for disease progression.
View Article and Find Full Text PDFThe conventional CaCl-HO phase diagram is often used to describe how calcium chloride behaves when it is used on a concrete pavement undergoing freeze-thaw damage. However, the chemistry of the concrete can alter the appropriateness of using the CaCl-HO phase diagram. This study shows that the Ca(OH) present in a hydrated portland cement can interact with CaCl solution creating a behavior that is similar to that observed in isoplethal sections of a ternary phase diagram for a Ca(OH)-CaCl-HO system.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
September 2015
Compensatory growth and regeneration of skeletal muscle is dependent on the resident stem cell population, satellite cells (SCs). Self-renewal and maintenance of the SC niche is coordinated by the paired-box transcription factor Pax7, and yet continued expression of this protein inhibits the myoblast differentiation program. As such, the reduction or removal of Pax7 may denote a key prerequisite for SCs to abandon self-renewal and acquire differentiation competence.
View Article and Find Full Text PDFBackground: Adult skeletal muscle regeneration is a highly orchestrated process involving the activation and proliferation of satellite cells, an adult skeletal muscle stem cell. Activated satellite cells generate a transient amplifying progenitor pool of myoblasts that commit to differentiation and fuse into multinucleated myotubes. During regeneration, canonical Wnt signalling is activated and has been implicated in regulating myogenic lineage progression and terminal differentiation.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
October 2013
Cardiomyocyte hypertrophy is the cellular response that mediates pathologic enlargement of the heart. This maladaptation is also characterized by cell behaviors that are typically associated with apoptosis, including cytoskeletal reorganization and disassembly, altered nuclear morphology, and enhanced protein synthesis/translation. Here, we investigated the requirement of apoptotic caspase pathways in mediating cardiomyocyte hypertrophy.
View Article and Find Full Text PDFProgrammed cell death (PCD) or apoptosis is a broadly conserved phenomenon in metazoans, whereby activation of canonical signal pathways induces an ordered dismantling and death of a cell. Paradoxically, the constituent proteins and pathways of PCD (most notably the metacaspase/caspase protease mediated signal pathways) have been demonstrated to retain non-death functions across all phyla including yeast, nematodes, drosophila, and mammals. The ancient conservation of both death and non-death functions of PCD proteins raises an interesting evolutionary conundrum: was the primordial intent of these factors to induce cell death or to regulate other cellular adaptations? Here, we propose the hypothesis that apoptotic behavior of PCD proteins evolved or were co-opted from core non-death functions.
View Article and Find Full Text PDFExpression of the cell surface sialomucin CD34 is common to many adult stem cell types, including muscle satellite cells. However, no clear stem cell or regeneration-related phenotype has ever been reported in mice lacking CD34, and its function on these cells remains poorly understood. Here, we assess the functional role of CD34 on satellite cell-mediated muscle regeneration.
View Article and Find Full Text PDFA major obstacle in performing multicenter controlled trials for pemphigus is the lack of a validated disease activity scoring system. Here, we assess the reliability and convergent validity of the PDAI (pemphigus disease area index). A group of 10 dermatologists scored 15 patients with pemphigus to estimate the inter- and intra-rater reliability of the PDAI and the recently described ABSIS (autoimmune bullous skin disorder intensity score) instrument.
View Article and Find Full Text PDFOur scientific knowledge of pemphigus has dramatically progressed in recent years. However, despite the availability of various therapeutic options for the treatment of inflammatory diseases, only a few multicenter controlled trials have helped to define effective therapies in pemphigus. A major obstacle in comparing therapeutic outcomes between centers is the lack of generally accepted definitions and measurements for the clinical evaluation of patients with pemphigus.
View Article and Find Full Text PDFA 21-year-old female-to-male transgender individual with a history of Crohn disease presented with enlarging perianal papules that initially were misdiagnosed as condyloma acuminatum. A biopsy specimen demonstrated granulomatous inflammation characteristic of Crohn disease. Although the patient's Crohn disease had been quiescent for years, a subsequent evaluation revealed the presence of a rectal stricture that was then dilated.
View Article and Find Full Text PDFPemphigus is a group of rare autoimmune mucocutaneous bullous diseases with potential significant morbidity and mortality. The two main subtypes are pemphigus vulgaris (PV) and pemphigus foliaceus (PF). Systemic corticosteroid use and other advances in management have dramatically decreased the mortality rate for pemphigus.
View Article and Find Full Text PDFObjectives: To evaluate the usefulness of integrated positron emission tomography and computed tomography (PET/CT) in staging mycosis fungoides (MF) and Sézary syndrome and to correlate PET/CT data with histopathologic diagnosis of lymph nodes (LNs).
Design: A single-center, prospective cohort analysis.
Setting: Academic referral center for cutaneous lymphoma.
Current data suggest that hormone replacement therapy (HRT) might have a beneficial role in the prevention of cardiovascular disease (CVD), osteoporosis, and dementia in postmenopausal women, but other therapies should be considered for the treatment of these conditions. In this review we evaluated the potential benefits of HRT for CVD, osteoporosis, and dementia, and compared HRT with proven, effective therapies. In addition, we identified the potential risks of breast and endometrial neoplasia, and an early risk of CVD and thromboembolic disease associated with HRT use.
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