## 1 Introduction  
Myocardial infarction (MI) caused by coronary artery disease is associated with significant mortality [1]. Clinical trials for the treatment of MI have provided irregular results so far; therefore, the induction of clinically useful therapeutic angiogenesis remain challenging [2, 3, 4]. Studies are necessary to understand the molecular mechanism of angiogenesis to develop therapeutics. There is a discrepancy related to the molecular signaling that increases angiogenesis and reduces ventricular remodeling in MI animals. MI-mediated downregulation of growth factors and increased oxidative stress led to impaired angiogenesis [5]. This creates a redox imbalance, which triggers stress-related complications in the system. The PHDs (prolyl hydroxylases) PHD1, PHD2 and PHD3 target HIF-1\(\alpha\) for degradation. Hypoxia or ischemia inactivates PHDs and results in HIF-1\(\alpha\) accumulation in the system [6, 7, 8]. Our previous findings [9] reported that deleting PHD1 and PHD-3 increased angiogenesis and blood perfusion in the murine hind-limb ischemia model by upregulating proangiogenic factor VEGF and HIF-1\(\alpha\). In addition, there was increased vessel density and increased protein expression, of BCI-2, in the PHD1 and PHD-3 ischemic limbs. In another study, PHD1 global knockout mice subjected to the ex vivo ischemia-reperfusion model (I/R model) also demonstrated preserved cardiac function in PHD1 mice compared to the corresponding wild-type controls [10]. In addition, our study with cardiac-specific PHD-2 knockout mice subjected to MI also demonstrated increased angiogenesis and heart function when compared to the wild-type controls [11]. When there is reduced oxygen (hypoxic or ischemic situation) in the system, both the subunits (HIF-1\(\alpha\) and HIF-2\(\alpha\)) move from the cytosol to the nucleus, where they dimerize with their respective subunits (HIF-1\(\alpha\) and HIF-2\(\beta\)) to form active transcription factor. This transcription factor's active form controls the regulation of hundreds of cellular genes, resulting in ischemic tissue regeneration, cell survival, and repair [12]. The HIF-1\(\alpha\) subunit controls HIF activity, while HIF-hydroxylases regulate the oxygen-dependent hydroxylation of the HIF-1\(\alpha\) subunit to limit its half-life. HIF-1\(\alpha\) is hydroxylated under normoxic conditions by PHDs. Hydroxylation by PHDs enables HIF-1\(\alpha\) proteasomal degradation via ubiquitination [13, 14]. Nearly, all PHDs have almost similar functions; however, they appear to have dissimilar specificities for various hydroxylation sites [15, 16]. HIF hydroxylases are the primary oxygen sensors in our system [15, 16, 17]. According to reports, a PHD inhibitor named GSK360A taken orally can protect the ischemic heart following myocardial infarction and increase HIF-1\(\alpha\) signaling [18]. Additionally, PHD1 knockdown decreased mouse liver ischemia-reperfusion injury [19]. Also, knockout of PHD1 stimulates skeletal muscle by altering base-level metabolism, thereby increasing hypoxic tolerance [20]. Our previous study demonstrated that PHD1 knockout (PHD1\({}^{-/-}\)) improved myocardial function after ischemia-reperfusion injury. The mechanism was likely due to HIF-1\(\alpha\) stabilization followed by angiogenic protein expression [21]. We also explored increased VEGF expression, angiogenic response, and vascularization in the murine hind-limb ischemia (HLI) model with PHD1\({}^{-/-}\) and PHD-3\({}^{-/-}\) mice compared to its wild-type counterpart [9]. However, further research or investigation is warranted using in vivo models of mouse MI and identifying differential gene expression to develop and understand the molecular mechanisms that underlie the knockout of PHD1. Our present approach in regulating HIF-1\(\alpha\) by inhibiting PHD1 may have been always associated with significant mortality strategic therapeutic potential for treating ischemic disorders, particularly in the heart.