The periostin was upregulated in neurons and capillary endothelial cells in the cerebral cortex at 24 h post-subarachnoid hemorrhage (SAH) and initiated BBB disruption, possibly via p38/ERK/MMP-9 signaling pathways and induction of tenascin-C [11].

Following transient cerebral ischemia, isoform 2 minimized the area of cerebral infarction displaying a neuroprotective role with phosphorylation of Akt [111]. Greater serum periostin levels were related to a larger cerebral infarction area and more serious neurological defects at 6-28 days following ischemia [14]. Toll-like receptor 4 (TLR4) selective blockade-IAXO-102 and clarithromycin inhibited BBB disruption and periostin expression [12,13].

Ang II evidently increased periostin through Ras/p38 MAPK (mitogen-activated protein kinase)/CREB and ERK/TGF-β1 pathways in myocytes and fibroblasts [123]. Detection of human tissue specimens reflected prominently high periostin expression in ischemic and reperfused tissue, as well as no expression in healthy myocardium [59]. The lineage analyses of mice verified that periostin-expressing CFs mainly derived from a mass of TCF21⁺ cells [124]. After MI, TGF-β1, mechanical pressure, and Cyclic AMP response element-binding protein 1 (CREB) stimulated cardiac fibroblasts, thereby augmenting ECM deposition, development of collagenous scar and cardiac remodeling, and release of periostin [125]. TGF-β1 upregulated periostin levels in CFs and vascular smooth muscle cells (VSMCs) employing Smad signaling pathways [126,127]. Periostin showed minimal levels under miR-203-3p-binding circumstances restricting cardiomyocytes apoptosis. However, the complex of periostin, miR-203-3p, and small nucleolar RNA host gene 8 (Snhg8) mediated neonatal mouse cardiomyocytes (NMCMs) apoptosis after hypoxia-treated NMCMs, contributing to acute myocardial infarction [66]. Treatment of MI with cardiac mesenchymal stem cells (MSCs) marked by Nestin demonstrated a greater effect on cardiac healing than bone marrow-derived MSCs (NesbmMSCs), which results from part involvement of periostin-induced M2 macrophage polarization [65]. In a rat MI model, Yoshiaki Taniyama et al. discovered four periostin isoforms, including isoforms 1, 2, 5, and 6. Isoform 1 decreased the attachment of fibroblasts and myocytes as well as facilitated myocyte death, leading to ventricular dilation and tissue remodeling. Blockade of exon 17 as prior target assists in protesting cardiac remodeling, diminishing fibrosis, ameliorating ejection fraction, and cardiac function eight weeks after MI [114]. Isoform 6 can mediate the migration of activated fibroblasts and the healing of impaired tissue by αv/FAK/AKT cascade [59]. The inhibition of periostin by valsartan might have an improved effect on cardiac remodeling after MI [57].

Release of periostin facilitated cardiomyocyte regeneration and angiogenesis by interacting with αvβ1, αvβ3, or αvβ5 integrins on myocytes and vascular endothelial cells to activate the PI3K-Akt pathways after MI. The treatment of animals with periostin patches (lacking the N-terminal signal peptide and C-terminal region) not only perfected cardiac fraction and ejection fraction but also contained fibrosis after MI [5]. Periostin eased inflammation and induced reentry of the cardiomyocytes cycle via TNF-α/NF-κB signaling transduction in conjunction with a declining caspase 7 activity [67]. Periostin ablation hindered myocardial regeneration by suppressing the PI3K/AKT/cyclin D1 transmission [68]. Another work in a mouse model of overexpressed full-length periostin indicated that periostin did not speed up the DNA synthesis of cardiomyocytes [128]. Further studies are needed to clarify these issues.

In diabetic rat hearts, periostin is noticeably overexpressed relative to healthy controls [79]. In the experimental autoimmune myocarditis (EAM) rats model, periostin was spotted in macrophages and fibroblasts. It elicited cardiac fibrosis, likely by recruiting immune cells [60]. A recent examination of atrial appendages from atrial fibrillation (AF) patients suggested a clear association between periostin levels of atrial tissues and deteriorated heart failure, as well as lessened ejection fraction [129]. MiR-30a and fibromodulin (FMOD) tempted the descent of periostin levels and the decrease of atrial fibrosis [61]. GSN, silencing P2Y1R, and slit2-Robo1 pathways inversely initiated periostin release, tempting fibrosis [62]. Periostin prompted pyroptosis by triggering the NLRP3/caspase-1 pathway during myocardial ischemia-reperfusion injury (MIRI) [56].

Valsartan and simvastatin (SIM) hindered periostin expression and alleviated pathologic remodeling [63,79]. Targeting of diabetic animals with the antioxidant resveratrol limited myofibroblast activation and downregulated the expression of periostin via suppressing ERK/TGF-β signaling [69].

Periostin expression intensively goes up in valvular interstitial cells (VICs) of the mitral valve, compared to wild-type mice. The mitral valve biopsies of male patients going through prosthetic surgery detected a pronounced enhancement in periostin in the ventricular [130]. Besides, periostin was firmly upregulated in the infiltrated inflammatory cells and myofibroblasts within patients with atherosclerotic or rheumatic valves. Meanwhile, massive periostin in the valve leaflet brings about extensive production of matrix metalloproteinase-2 (MMP-2) and MMP-9, leading to severe fibrosis in atherosclerotic and rheumatic VHD [64]. Periostin also prompted the osteogenic potential of aortic valve calcification [131].

Atrial natriuretic peptide (ANP) inhibited periostin expression in the VSMCs and cardiac fibroblasts [70], but oxidative stress contributes to periostin production [132]. The increase in periostin augmented the differentiation and migration of VSMCs [133].

In a hyperlipidemia-associated model of rats, periostin upregulation caused calcium deposits through the successive inhibition of p53 and SLC7A11 in VSMCs [71]. Additionally, plasma periostin levels were positively connected with the Agatston score in patients with coronary artery calcification (CAC). Periostin promoted glycolysis and mitochondrial malfunction as well as contained peroxisome proliferation-activated receptor γ(PPARγ) in VSMCs, thereby provoking arterial calcification [58].