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Cardiac Tumours
Published in Mary N. Sheppard, Practical Cardiovascular Pathology, 2022
Cardiac sarcomas which are not angiomatous or rhabdomyomatous show a very wide range of differentiation patterns including striated muscle, smooth muscle, fibroblastic, mesothelial neural, osteogenic, myxoid and liposarcoma. In the majority of the sarcomas, the predominant pattern is that of an undifferentiated sarcoma and many histological blocks have to be taken to recognize a particular phenotypic expression. Myxoid change in sarcomas is common and may be misdiagnosed as myxoma if involving the atrial wall but hypercellularity, pleomorphism and mitoses will make the difference. As already stated, these tumours do not express calretinin as do myxomas, and other markers are also negative, apart from vimentin and smooth muscle actin. Some sarcomas show more than one differentiation pattern. Desmin expression suggests myoid differentiation. Vimentin marks virtually every sarcoma and is nondiscriminatory as is smooth muscle actin. S-100 will identify neural and fat tumours. Use of muscle markers, muscle-specific actin, desmin and myogenin, and focally with fast-myosin and sarcomeric actin, as well as calponin and WT-1, point to rhabdomyosarcoma. Electron microscopy may also be useful indicating specific differentiation but is rarely used today. Most of the gene alterations associated with sarcomas are chromosomal translocations. Cardiac sarcomas typically have genetic profiles with recurrent alterations in MDM2, PDGFRA or EGFR, which have potential as future therapeutic targets.
Functional Properties of Muscle
Published in Nassir H. Sabah, Neuromuscular Fundamentals, 2020
Excitation-contraction coupling is different in smooth muscle from that in skeletal muscle. Smooth muscle lacks T tubules, since the small cell size, the slow contraction, the lack of organization of myofibrils, and the absence of APs in many cases, do not warrant a T tubule system. Smooth muscle lacks troponin but has, instead, two other thin filament proteins, caldesmon and calponin. On stimulation, contraction is initiated by Ca2+ influx from the extracellular fluid as well as the SR, the relative contribution of these sources differs between different smooth muscle. Ca2+ influx from the SR occurs in some locations through a close association between the SR membrane and the sarcolemma, analogous to that of T tubules in skeletal muscle, as well as through second messengers (Section 6.3) that are released upon stimulation and which cause opening of Ca2+ channels in the SR membrane. The total amount of Ca2+ released by a single stimulus is usually sufficient to activate only a fraction of the cross bridges available, which allows variation in Ca2+ concentration to grade the force produced by the muscle. In the absence of an AP, Ca2+ concentration can be graded by membrane depolarization or hyperpolarization.
Ca2+ Modulation System of Myometrial Contraction During Gestation
Published in Robert E. Garfield, Thomas N. Tabb, Control of Uterine Contractility, 2019
Phorbol ester increases sensitization of the contractile apparatus without change of [Ca2+]i in rabbit mesenteric artery, porcine coronary artery, or pregnant rat myometrium.34,35,72 Activation of protein kinase C by stimulation with phorbol ester has been reported to result in MLC phosphorylation at sites other than serine-19.4,6 It has been also reported that contractions elicited by agonists that trigger phosphoinositide turnover do not involve PKC-catalyzed phosphorylation of either myosin or MLCK.4 Recently, it has been demonstrated that the putative thin-filament regulatory proteins, calponin and caldesmon, may be involved in the agonist-induced increase in myofilament Ca2+ sensitivity. Unphosphorylated calponin and caldesmon bind to actin and depress actin-activated myosin ATPase activity.62,81 In rabbit myometrium caldesmon inhibits myosin ATPase activity.55 Translocation of PKC to the sarcolemma activated by agonist is considered to result in phosphorylation of caldesmon and calponin to produce slow sustained contractions.4,62,81 Thus, increased protein kinase C activity may therefore relieve the inhibitory effects of calponin or caldesmon and account for phorbol ester-induced increase in force shown in our study.
Deletion of Calponin 2 Reduces the Formation of Postoperative Peritoneal Adhesions
Published in Journal of Investigative Surgery, 2022
Tzu-Bou Hsieh, Han-Zhong Feng, Jian-Ping Jin
Calponin is an actin-binding protein that regulates the structure and function of actin cytoskeleton through inhibiting actin-activated myosin ATPase and motor activities [13–15]. Three isoforms of calponin, calponins 1, 2, and 3, are present in vertebrates encoded by homologous genes, Cnn1, Cnn2, and Cnn3, respectively [16, 17]. Calponin 1 is expressed exclusively in smooth muscle and functions to regulate smooth muscle contractility [16, 18–20]. Calponin 2 is expressed in smooth muscles and in non-muscle cells such as epithelial cells, endothelial cells, myeloid blood cells and fibroblasts [18, 21, 22] with functions in regulating cell proliferation, adhesion, migration and phagocytosis [16, 17]. Calponin 3 is found in smooth muscle, brain, trophoblasts, and B-lymphocytes with a function of regulating development, growth and cell fusion [23–27].
Neuropsychiatric manifestations in primary Sjogren syndrome
Published in Expert Review of Clinical Immunology, 2022
Simone Appenzeller, Samuel de Oliveira Andrade, Mariana Freschi Bombini, Samara Rosa Sepresse, Fabiano Reis, Marcondes C. França
Calponin −3 is an actin – binding protein expressed in satellite cells and several other tissues, including skeletal muscle, cartilage, brain, and trophoblasts, among others [70]. In pSS, anti -calponin-3 antibodies have been described to occur in pSS in 11%, associated with peripheral neuropathy, especially non-length dependent small-fiber neuropathies, and large-fiber sensory neuronopathies [71].
Targeting the cytoskeleton and extracellular matrix in cardiovascular disease drug discovery
Published in Expert Opinion on Drug Discovery, 2022
Bohdan B. Khomtchouk, Yoon Seo Lee, Maha L. Khan, Patrick Sun, Deniel Mero, Michael H. Davidson
More recent research further supports the potential for calponin 2 to be an effective cytoskeletal target for cardiovascular diseases. Given the shared characteristics between atherosclerosis and calcific aortic valve disease (CAVD), the most common heart valve disease in the western world, Plazyo and colleagues (2018) investigated the role of calponin 2 in CAVD [72]. CAVD is characterized by fibrotic thickening along with both aortic sclerosis and stenosis, which eventually leads to congestive HF, but despite its common occurrence, there were no non-surgical treatments hence the researchers’ focus on calponin 2 [72]. The results of this study showed that deletion of the calponin 2 gene reduced calcification in ApoE knockout mice [72]. Plazyo and colleagues concluded that calponin 2ʹs role in the differentiation of aortic valve interstitial cells (AVICs) is a major step in the development of CAVD [72]. These findings provide additional support to the hypothesis that the cytoskeleton is dysregulated during CVD progression. In summary, Plazyo and coworkers (2018) concluded: ‘Because calponin 2 acts as a direct modulator of actin and actin-dependent cellular functions, targeting calponin 2 may be a way to manipulate cytoskeleton activity for altering mechanoregulation in the treatment of diseases involving dysregulated mechanical signaling, such as CAVD. Thus, this therapeutic promise merits further investigation.’ The aforementioned findings are notable because of calponin 2ʹs direct role in cytoskeletal function. Hossain and coworkers (2005) suggested that calponin 2 interacts with actin cytoskeleton function through its association with tropomyosin, which is colocalized with calponin 2 in actin stress fibers [73]. The study also showed that calponin 2 protects actin filaments from cytochalasin B, which inhibits polymerization by binding to the barbed end, and demonstrates the stability of the actin filaments [73]. Overall, these studies suggest that calponin 2 is a viable cytoskeletal drug target that merits further research in other CVDs.