Peiying Zhang

Risk of cardiovascular disease in inflammatory bowel disease (Review)

Cardiovascular disease (CVD) can arise because of chronic inflammation and inflammatory bowel disease (IBD) is one such disease where the risk for CVD and eventual heart failure is increased considerably. The incidence of IBD, which refers to both ulcerative colitis and Crohns disease, has been on the increase in several countries and is a potential risk factor for CVD. Although IBD can potentially cause venous thromboembolism, its significance in arterial stiffening, atherosclerosis, ischemic heart disease and myocardial infarction is only being realized now and it is currently under debate. However, several studies with large groups of patients have demonstrated the association of IBD with heart disease. It has been suggested that systemic inflammation as observed in IBD patients leads to oxidative stress and elevated levels of inflammatory cytokines such as tumor necrosis factor-α (TNF-α), which lead to phenotypic changes in smooth muscle cells and sets into motion a series of events that culminate in atherosclerosis and CVD. Besides the endogenous factors and cytokines, it has been suggested that due to the compromised intestinal mucosal barrier, endotoxins and bacterial lipopolysaccharides produced by intestinal microflora can enter into circulation and activate inflammatory responses that lead to atherosclerosis. Therapeutic management of IBD-associated heart diseases cannot be achieved with simple anti-inflammatory drugs such as corticosteroids and anti-TNF-α antibodies. Treatment with existing medications for CVDs, aspirin, platelet aggregation inhibitors and statins is found to be acceptable and safe. Nevertheless, further research is needed to assess their efficacy in IBD patients suffering from heart disease.

Transforming growth factor β and its role in heart disease (Review)

Myocardial infarction (MI) is a major form of heart disease that leads to immediate cardiomyocyte death due to ischemia and eventually fibrosis and scar formation and further dysfunction of myocardium and heart failure. Extracellular matrix (ECM) production and tissue repair is conducted by myofibroblasts, which are formed from the normal quiescent cardiac fibroblasts following transformational changes, through the active participation of transforming growth factor β (TGFβ) and its signaling pathways. TGFβ appears to be a ‘Master of all trades’, with respect to cardiac fibrosis, as it can promote cardiomyocyte apoptosis and cardiac hypertrophy. TGFβ signaling involves its binding to TGFβ receptor type II (TGFβRII), which recruits TGFβ receptor type I (TGFβRI), which are also known as activin receptor-like kinase (ALK) in five different isoforms. In canonical signaling pathways, ALK5 activates Smads 2 and 3, and ALK1 activates Smads 1 and 5. These pairs of Smads form a corresponding complex and then bind to Smad 4, to translocate into the nucleus, where transcriptional reprogramming is carried out to promote myofibroblast formation and ECM production, eventually leading to cardiac fibrosis. TGFβ levels are elevated in MI, thereby aggravating the myocardial injury further. Several microRNAs are involved in the regulation of TGFβ signaling at different steps, affecting different components. Therapeutic targeting of TGFβ signaling at ALK1-5 receptor activity level has met with limited success and extensive research is needed to develop therapies based on the components of TGFβ signaling pathway, for instance cardiac dysfunction and heart failure.

Pathophysiology of valvular heart disease

Valvular heart disease (VHD) is caused by either damage or defect in one of the four heart valves, aortic, mitral, tricuspid or pulmonary. Defects in these valves can be congenital or acquired. Age, gender, tobacco use, hypercholesterolemia, hypertension, and type II diabetes contribute to the risk of disease. VHD is an escalating health issue with a prevalence of 2.5% in the United States alone. Considering the likely increase of the aging population worldwide, the incidence of acquired VHD is expected to increase. Technological advances are instrumental in identifying congenital heart defects in infants, thereby adding to the growing VHD population. Almost one-third of elderly individuals have echocardiographic or radiological evidence of calcific aortic valve (CAV) sclerosis, an early and subclinical form of CAV disease (CAVD). Of individuals ages >60, ~2% suffer from disease progression to its most severe form, calcific aortic stenosis. Surgical intervention is therefore required in these patients as no effective pharmacotherapies exist. Valvular calcium load and valve biomineralization are orchestrated by the concerted action of diverse cell-dependent mechanisms. Signaling pathways important in skeletal morphogenesis are also involved in the regulation of cardiac valve morphogenesis, CAVD and the pathobiology of cardiovascular calcification. CAVD usually occurs without any obvious symptoms in early stages over a long period of time and symptoms are identified at advanced stages of the disease, leading to a high rate of mortality. Aortic valve replacement is the only primary treatment of choice. Biomarkers such as asymmetric dimethylarginine, fetuin-A, calcium phosphate product, natriuretic peptides and osteopontin have been useful in improving outcomes among various disease states. This review, highlights the current understanding of the biology of VHD, with particular reference to molecular and cellular aspects of its regulation. Current clinical questions and the development of new strategies to treat various forms of VHD medically were addressed.

PCSK9 as a therapeutic target for cardiovascular disease (Review)

It is well recognized that the elevated plasma level of low-density lipoprotein-cholesterol (LDL-C) is a major risk factor for atherosclerosis and cardiovascular disease (CVD). Deposition of pro-atherogenic LDL-C, on the intima of arterial wall, contributes to plaque formation and atherosclerosis, which further leads to lowered blood flow to vital organs and increased risk of CVD. The most commonly used statin therapy is effective in reducing dyslipidemia and preventing cardiovascular events only in about half of the patient population. However, in patients with familial hypercholesterolemia, these drugs were not effective to meet the required goals of lower LDL-C, and to reduce the CVD risk. Furthermore, many patients even develop intolerability to statins and resistance. The identification of pro-protein convertase subtilisin/kexin type 9 (PCSK9) and the association of PCSK9 mutations with familial hypercholesterolemia led to the identification of PCSK9 as a new therapeutic target for lowering LDL-C and dyslipidemia-associated CVD. PCSK9 is found to promote the degradation of LDL-receptor (LDLR), thus rendering it unavailable for recycling to hepatocyte plasma membrane, leading to elevated levels of circulating LDL-C, as it cannot be taken up into cells. While gain-of-function mutations aggravate the degradation of LDLR as in familial hypercholesterolemia whereas loss of function mutations reduce the ability of PCSK9 to promote the degradation of LDLR and thus lower the plasma level of LDL-C and dyslipidemia. Monoclonal antibodies against PCSK9 are currently being tested in clinical trials and are found to be efficacious in countering the activity of PCSK9 and thus control the plasma LDL-C and triglycerides even in statin non-responsive patients and protect against dyslipidemia-related CVD.

Vitamin D nutritional status and the risk for cardiovascular disease.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality. CVD has a significant impact on health care systems worldwide and over 23 million individuals are expected to succumb to the disease by 2030. Early onset of atherosclerosis in childhood along with other risk factors of CVD, including elevated circulating lipids, have been shown to persist in adulthood and lead to CVD. Vitamin D deficiency is considered a risk factor for the pathogenesis of CVD, with childhood nutritional status of vitamin D being an important determinant of the development of CVD. Low levels of 25-hydroxyvitamin D can arise due to reduced intake as well as geographical location, and other diseases/conditions such as chronic kidney disease and obesity. Childhood vitamin D deficiency can progress and lead to atherosclerosis and other CVDs in adulthood. Early intervention with vitamin D supplementation is an ideal approach towards preventive therapy. However, there is no clear consensus regarding the role of vitamin D in childhood CVD. In the present study, we reviewed the available evidence in favor of and against such a role for this vitamin.

Recent perspectives of electronic medical record systems.

Implementation of electronic medical record (EMR) systems within developing contexts as part of efforts to monitor and facilitate the attainment of health-related aims has been on the increase. However, these efforts have been concentrated on urban hospitals. Recent findings showed that development processes of EMR systems are associated with various discrepancies between protocols and work practices. These discrepancies were mainly caused by factors including high workload, lack of medical resources, misunderstanding of the protocols by health workers, and client/patient practices. The present review focused on the effects of EMRs on patient care work, and on appropriate EMR designs principles and strategies to ameliorate these systems.

Protective approaches against myocardial ischemia reperfusion injury.

Myocardial ischemia-reperfusion is the leading cause for the events of cardiovascular disease, and is considered as a major contributor to the morbidity and mortality associated with coronary occlusion. The myocardial damage caused by ischemia-reperfusion injury constitutes the primary pathological manifestation of coronary artery disease. It results from the interaction between the substances that accumulate during ischemia and those that are delivered on reperfusion. The level of this damage can range from a small insult resulting in limited myocardial damage to a large injury culminating in myocyte death. Importantly, major ischemia-reperfusion injury to the heart can result in permanent disability or death. Given the worldwide prevalence of coronary artery disease, developing a strategy to provide cardioprotection against ischemia-reperfusion-induced damage is of great importance. Currently, the treatment of reperfusion injury following ischemia is primarily supportive, since no specific target-oriented therapy has been validated thus far. Nevertheless, therapeutic approaches to protect against myocardial ischemia-reperfusion injury remain an active area of investigation given the detrimental effects of this phenomenon.

hsCRP and ET-1 expressions in patients with no-reflow phenomenon after percutaneous coronary intervention

Objective: To explore hsCRP and ET-1 expressions in patients with no-reflow phenomenon after percutaneous coronary intervention (PCI). Methods: A total of 136 patients with single coronary artery disease receiving PCI were divided into a reflow group and a no-reflow group to compare the level use of ET-1 alone with combined level of ET-1 and hs-CRP in PCI regarding sensitivity, specificity, positive and negative predictive values and accuracy for postoperative no-reflow. The study was conducted between 2014-2016 at our hospital. Results: Postoperative levels of ET-1 and hs-CRP in no-reflow group were significantly higher than those of reflow group (P<0.05). ET-1 level of reflow group peaked three hours after PCI and then declined. Serum level of hs-CRP decreased most obviously within three hours after PCI in reflow group and three hours - three days after PCI in no-reflow group. Left ventricular end-diastolic diameters of both groups after PCI were apparently lower than those before PCI, without significant inter-group difference (P>0.05). Left ventricular end-systolic diameters and left ventricular ejection fractions of both groups evidently increased after PCI, without significant inter-group differences either (P>0.05). Corrected TIMI frame count (CTFC) and wall motion score index of reflow group after PCI were significantly lower than those of no-reflow group (P<0.05). ET-1 level was positively correlated with CTFC (P<0.05). Multivariate linear regression showed hs-CRP was negatively correlated with the serum level (P<0.05) (r=-0.34). Conclusion: hsCRP and ET-1 levels significantly increased in patients with no-reflow phenomenon.

Recent perspectives of stem cell use in cardiac disorders

Stem cells and progenitor cells have unique abilities for self-renewal. These cells have the differentiation capacity to develop as various types of cells, including cardiac cells. Because atherosclerosis is considered a disease of endothelial dysfunction, regenerative cell-based therapy is an effective approach to ameliorate atherosclerotic pathogenesis. Recent studies are now focused on the effective targeting of stem cells to the site of interest. The echogenic liposome approach has good potential for efficiently delivering drugs as well as the ability to reduce atheroma progression. The present review article enhances recent perspectives on the stem cell approach, including new delivery approaches for cardiac disorders.

Cardiac complications in cancer treatment- a review

Cardiac dysfunction is often associated with effective cancer treatment. A number of targeted therapies against cancer have been observed to cause cardiac dysfunction. In some instances, a patient may outlive his or her cancer but die due to heart failure. Recent research has been focused on the development of new avenues and technological advancements to monitor clinical cardiotoxicity and cardiac dysfunction due to anticancer treatment. These newer treatment options are also increasingly effective and are focused more on post-cancer life. The present review article expands the current view of cardiac complications involved in cancer treatment along with the recent developments in the area.