J. Cardiovasc. Dev. Dis., Volume 6, Issue 2 (June 2019) – 11 articles

Mammalian Kiaa1211 and Kiaa1211-like are a homologous pair of uncharacterized, highly conserved genes cloned from fetal and adult brain cDNA libraries. Herein we map the in utero spatiotemporal expression of mKiaa1211 and mKiaa1211L mRNA and their expression patterns in postnatal testis, skin, gastrointestinal, and adipose progenitor tissues. Significantly, mKiaa1211 is present throughout the early stages of mouse heart development, particularly in the second heart field (SHF) lineage as it differentiates from mesenchymal cells into cardiomyocytes. We also show that mKiaa1211 is expressed within several early neuronal tissues destined to give rise to central, peripheral, and sympathetic nervous system structures. Expression profiling revealed that the paralog mKiaa1211L is not expressed during the normal developmental process and that mKiaa1211 expression was noticeably absent from most adult terminally differentiated tissues. Finally, we confirm that a previously uncharacterized CRISPR/CAS-generated mKiaa1211 mouse mutant allele is hypomorphic. Full article

The American Heart Association has published a scientific statement on the effect of hookah smoking on health outcomes; nevertheless, hookah smoking continues to be popular worldwide, especially among the young. Recent reports mention a potential link between hookah smoking and obesity; however, uncertainties still surround this issue. The aim of the current study was to conduct a systematic review to clarify whether hookah smoking is associated with a higher risk of obesity among the general population. This study was conducted in compliance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, and data were collated by means of a meta-analysis and a narrative synthesis. Of the 818 articles retrieved, five large-population and low-bias studies comprising a total of 16,779 participants met the inclusion criteria and were reviewed. All included studies reported that, regardless of gender, hookah smoking increases the risk of obesity among all ages and observed an association between the two after a correction for several confounders or reported a higher prevalence of obesity among hookah smokers. This was confirmed by the meta-analysis. Therefore, hookah smoking seems to be associated with a higher risk of obesity. Public health policymakers should be aware of this for the better management of obesity and weight-related comorbidities. Full article

Ischemic preconditioning (IPC) and activation of ATP-sensitive potassium channels (K_ATP) protect cardiac myocytes from ischemia reperfusion (IR) injury. We investigated the influence of IR injury, IPC and K_ATP in isolated rat cardiac fibroblasts. Hearts were removed under isoflurane anesthesia. IR was simulated in vitro by application and removal of paraffin oil over pelleted cells. Ischemia (30, 60 and 120 min) followed by 60 min reperfusion resulted in significant differentiation of fibroblasts into myofibroblasts in culture (mean % fibroblasts ± SEM in IR vs. time control: 12 ± 1% vs. 63 ± 2%, 30 min ischemia; 15 ± 3% vs. 71 ± 4%, 60 min ischemia; 8 ± 1% vs. 55 ± 2%, 120 min ischemia). IPC (15 min ischemia, 30 min reperfusion) significantly attenuated IR-induced fibroblast differentiation (52 ± 3%) compared to 60 min IR. IPC was mimicked by opening K_ATP with pinacidil (50 μM; 43 ± 6%) and by selectively opening mitochondrial K_ATP (mK_ATP) with diazoxide (100 μM; 53 ± 3%). Furthermore, IPC was attenuated by inhibiting K_ATP with glibenclamide (10 μM; 23 ± 5%) and by selectively blocking mK_ATP with 5-hydroxydecanoate (100 μM; 22 ± 9%). These results suggest that (a) IR injury evoked cardiac fibroblast to myofibroblast differentiation, (b) IPC attenuated IR-induced fibroblast differentiation, (c) K_ATP were involved in IPC and (d) this protection involved selective activation of mK_ATP. Full article

Congenital heart disease (CHD) arises due to errors during the embryonic development of the heart, a highly regulated process involving an interplay between cell-intrinsic transcription factor expression and intercellular signalling mediated by morphogens. Emerging evidence indicates that expression of these protein-coding genes is controlled by a plethora of previously unappreciated non-coding RNAs operating in complex feedback-control circuits. In this review, we consider the contribution of long non-coding RNA (lncRNA) to embryonic cardiovascular development before discussing applications to CHD diagnostics and therapeutics. We discuss the process of lineage restriction during cardiovascular progenitor cell differentiation, as well as the subsequent patterning of the cardiogenic progenitor fields, taking as an example the regulation of NODAL signalling in left-right patterning of the heart. lncRNA are a highly versatile group. Nuclear lncRNA can target specific genomic sequences and recruit chromatin remodelling complexes. Some nuclear lncRNA are transcribed from enhancers and regulate chromatin looping. Cytoplasmic lncRNA act as endogenous competitors for micro RNA, as well as binding and sequestering signalling proteins. We discuss features of lncRNA that limit their study by conventional methodology and suggest solutions to these problems. Full article

The interleukin-1 family is associated with innate immunity and inflammation. The latter has been linked to the genesis of cardiovascular diseases. We, therefore, investigated whether interleukin-1 beta (IL-1β) is activated during arterialization of vein grafts. First, we examined the activation of IL-1β using the rat arterialized jugular vein serially sampled for up to 90 days. IL-1β expression increased 18 times on day 1 in the arterialized rat jugular vein and remained five times above nonarterialized vein levels for up to 90 days. Similarly, IL-1β expression increased early (1–5 days) in human vein graft autopsy samples compared with late phases (1–4 years). Activation was also detected in ex vivo arterialized human saphenous veins. Upon stratification of the results, we uncovered a T allele promoter attenuating effect in IL-1β activation in response to hemodynamic stress. Altogether, the results show that IL-1β is activated during arterialization of vein grafts in rats and humans, and this response is modulated by -511C/T IL-1β gene polymorphism. It is tempting to speculate that the activation of IL-1β, and consequently local inflammation, modulates early vascular remodeling and that the gene polymorphism may be useful in predicting outcomes or assisting in interventions. Full article

The aging and elderly population are particularly susceptible to cardiovascular disease. Age is an independent risk factor for cardiovascular disease (CVD) in adults, but these risks are compounded by additional factors, including frailty, obesity, and diabetes. These factors are known to complicate and enhance cardiac risk factors that are associated with the onset of advanced age. Sex is another potential risk factor in aging adults, given that older females are reported to be at a greater risk for CVD than age-matched men. However, in both men and women, the risks associated with CVD increase with age, and these correspond to an overall decline in sex hormones, primarily of estrogen and testosterone. Despite this, hormone replacement therapies are largely shown to not improve outcomes in older patients and may also increase the risks of cardiac events in older adults. This review discusses current findings regarding the impacts of age and gender on heart disease. Full article

There is increasing recognition of a specific diabetic cardiomyopathy beyond ischemic cardiomyopathy, which leads to structural and functional myocardial abnormalities. The aim of this review is to summarize the recent literature on diagnostic findings and prognostic significance of non-invasive imaging including echocardiography, nuclear imaging, computed tomography and cardiovascular magnetic resonance in diabetic cardiomyopathy. Full article

Cardiovascular disease (CVD) is a major public health problem in Saudi Arabia. Dietary intake plays a major role in CVD incidence; however, the dietary intake status in Saudi nationals with CVD is unknown. We aimed to investigate whether the dietary patterns of Saudi males, using the Saudi dietary guidelines adherence score, in parallel with the measurement of a selective number of cardiovascular disease-related biomarkers, are contributing factors to CVD risk. Demographics, dietary adherence score, and blood biomarker levels were collected for 40 CVD patients and forty non-CVD patients. Fasting blood glucose (p = 0.006) and high-density lipoprotein levels (p = 0.03) were significantly higher in CVD patients. The adherence score to the Saudi dietary guidelines was not significantly different between the CVD and non-CVD patients; however, the specific adherence scores of fruit (p = 0.02), olive oil (p = 0.01), and non-alcoholic beer (p = 0.02) were significantly higher in the non-CVD patients. The differences in CVD family history (p = 0.02) and adherence scores to specific groups/foods between the CVD and non-CVD patients may contribute to CVD risk in Saudi males. However, as the sample size of this study was small, further research is required to validate these findings. Full article

The let-7c family of micro-RNAs (miRNAs) is expressed during embryonic development and plays an important role in cell differentiation. We have investigated the role of let-7c in heart regeneration after injury in adult zebrafish. let-7c antagomir or scramble injections were given at one day after cryoinjury (1 dpi). Tissue samples were collected at 7 dpi, 14 dpi and 28 dpi and cardiac function was assessed before cryoinjury, 1 dpi, 7 dpi, 14 dpi and 28 dpi. Inhibition of let-7c increased the rate of fibrinolysis, increased the number of proliferating cell nuclear antigen (PCNA) positive cardiomyocytes at 7 dpi and increased the expression of the epicardial marker raldh2 at 7 dpi. Additionally, cardiac function measured with echocardiography recovered slightly more rapidly after inhibition of let-7c. These results reveal a beneficial role of let-7c inhibition in adult zebrafish heart regeneration. Full article

Cardiovascular development is a complex developmental process starting with the formation of an early straight heart tube, followed by a rightward looping and the configuration of atrial and ventricular chambers. The subsequent step allows the separation of these cardiac chambers leading to the formation of a four-chambered organ. Impairment in any of these developmental processes invariably leads to cardiac defects. Importantly, our understanding of the developmental defects causing cardiac congenital heart diseases has largely increased over the last decades. The advent of the molecular era allowed to bridge morphogenetic with genetic defects and therefore our current understanding of the transcriptional regulation of cardiac morphogenesis has enormously increased. Moreover, the impact of environmental agents to genetic cascades has been demonstrated as well as of novel genomic mechanisms modulating gene regulation such as post-transcriptional regulatory mechanisms. Among post-transcriptional regulatory mechanisms, non-coding RNAs, including therein microRNAs and lncRNAs, are emerging to play pivotal roles. In this review, we summarize current knowledge on the functional role of non-coding RNAs in distinct congenital heart diseases, with particular emphasis on microRNAs and long non-coding RNAs. Full article

In its classical view, the renin angiotensin system (RAS) was defined as an endocrine system involved in blood pressure regulation and body electrolyte balance. However, the emerging concept of tissue RAS, along with the discovery of new RAS components, increased the physiological and clinical relevance of the system. Indeed, RAS has been shown to be expressed in various tissues where alterations in its expression were shown to be involved in multiple diseases including atherosclerosis, cardiac hypertrophy, type 2 diabetes (T2D) and renal fibrosis. In this chapter, we describe the new components of RAS, their tissue-specific expression, and their alterations under pathological conditions, which will help achieve more tissue- and condition-specific treatments. Full article