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Myocardial infarction (MI), as a result of thrombosis or vascular occlusion, is the most prevalent cause of morbidity and mortality among all cardiovascular diseases. The devastating consequences of MI are compounded by the complexities of cellular functions involved in the initiation and resolution of early-onset inflammation and the longer-term effects related to scar formation. The resultant tissue damage can occur as early as 1 h after MI and activates inflammatory signalling pathways to elicit an immune response. Macrophages are one of the most active cell types during all stages after MI, including the cardioprotective, inflammatory and tissue repair phases. In this Review, we describe the phenotypes of cardiac macrophage involved in MI and their cardioprotective functions. A specific subset of macrophages called resident cardiac macrophages (RCMs) are derived from yolk sac progenitor cells and are maintained as a self-renewing population, although their numbers decrease with age. We explore sophisticated sequencing techniques that demonstrate the cardioprotective properties of this cardiac macrophage phenotype. Furthermore, we discuss the interactions between cardiac macrophages and other important cell types involved in the pathology and resolution of inflammation after MI. We summarize new and promising therapeutic approaches that target macrophage-mediated inflammation and the cardioprotective properties of RCMs after MI. Finally, we discuss future directions for the study of RCMs in MI and cardiovascular health in general., (© 2023. Springer Nature Limited.)

The hallmark of severe COVID-19 involves systemic cytokine storm and multi-organ injury including testicular inflammation, reduced testosterone, and germ cell depletion. The ACE2 receptor is also expressed in the resident testicular cells, however, SARS-CoV-2 infection and mechanisms of testicular injury are not fully understood. The testicular injury could be initiated by direct virus infection or exposure to systemic inflammatory mediators or viral antigens. We characterized SARS-CoV-2 infection in different human testicular 2D and 3D culture systems including primary Sertoli cells, Leydig cells, mixed seminiferous tubule cells (STC), and 3D human testicular organoids (HTO). Data shows that SARS-CoV-2 does not productively infect any testicular cell type. However, exposure of STC and HTO to inflammatory supernatant from infected airway epithelial cells and COVID-19 plasma decreased cell viability and resulted in the death of undifferentiated spermatogonia. Further, exposure to only SARS-CoV-2 Envelope protein caused inflammatory response and cytopathic effects dependent on TLR2, while Spike 1 or Nucleocapsid proteins did not. A similar trend was observed in the K18-hACE2 transgenic mice which demonstrated a disrupted tissue architecture with no evidence of virus replication in the testis that correlated with peak lung inflammation. Virus antigens including Spike 1 and Envelope proteins were also detected in the serum during the acute stage of the disease. Collectively, these data strongly suggest that testicular injury associated with SARS-CoV-2 infection is likely an indirect effect of exposure to systemic inflammation and/or SARS-CoV-2 antigens. Data also provide novel insights into the mechanism of testicular injury and could explain the clinical manifestation of testicular symptoms associated with severe COVID-19., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Giannakopoulos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: Congenital hypopituitarism usually occurs sporadically. In most patients, the etiology remains unknown., Methods: We studied 13 children with sporadic congenital hypopituitarism. Children with non-endocrine, non-familial idiopathic short stature (NFSS) ( n = 19) served as a control group. Exome sequencing was performed in probands and both unaffected parents. A burden testing approach was used to compare the number of candidate variants in the two groups., Results: First, we assessed the frequency of rare, predicted-pathogenic variants in 42 genes previously reported to be associated with pituitary gland development. The average number of variants per individual was greater in probands with congenital hypopituitarism than those with NFSS (1.1 vs. 0.21, mean variants/proband, P = 0.03). The number of probands with at least 1 variant in a pituitary-associated gene was greater in congenital hypopituitarism than in NFSS (62% vs. 21%, P = 0.03). Second, we assessed the frequency of rare, predicted-pathogenic variants in the exome (to capture undiscovered causes) that were inherited in a fashion that could explain the sporadic occurrence of the proband's condition with a monogenic etiology ( de novo mutation, autosomal recessive, or X-linked recessive) with complete penetrance. There were fewer monogenic candidates in the probands with congenital hypopituitarism than those with NFSS (1.3 vs. 2.5 candidate variants/proband, P = 0.024). We did not find any candidate variants (0 of 13 probands) in genes previously reported to explain the phenotype in congenital hypopituitarism, unlike NFSS (8 of 19 probands, P = 0.01)., Conclusion: Our findings provide evidence that the etiology of sporadic congenital hypopituitarism has a major genetic component but may be infrequently monogenic with full penetrance, suggesting a more complex etiology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer MD declared a past co-authorship with one of the authors JB to the handling editor., (Copyright © 2021 Jee, Gangat, Yeliosof, Temnycky, Vanapruks, Whalen, Gourgari, Bleach, Yu, Marshall, Yanovski, Link, Ten, Baron and Radovick.)